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In a prospective cohort of subjects who subsequently developed preeclampsia (PE, n = 14) versus remaining healthy (NORM, n = 12), early gestation circulating extracellular vesicles (EVs) containing a panel of microRNA signatures were characterized and their biological networks of targets deciphered. Multiple microRNAs of which some arose from the placenta (19MC and 14MC) demonstrated changes in association with advancing gestation, while others expressed were pathognomonic of the subsequent development of characteristic clinical features of PE which set in as a late-onset subtype. This panel of miRNAs demonstrated a predictability with an area under the curve of 0.96 using leave-one-out cross-validation training in a logistic regression model with elastic-net regularization and precautions against overfitting. In addition, this panel of miRNAs, some of which were previously detected in either placental tissue or as maternal cell-free non-coding transcripts, lent further validation to our EV studies and the observed association with PE. Further, the identified biological networks of targets of these detected miRNAs revealed biological functions related to vascular remodeling, cellular proliferation, growth, VEGF, EGF and the PIP3/Akt signaling pathways, all mediating key cellular functions. We conclude that we have demonstrated a proof-of-principle by detecting a panel of EV packaged miRNAs in the maternal circulation early in gestation with possibilities of biological function in the placenta and other maternal tissues, along with the probability of predicting the subsequent clinical appearance of PE, particularly the late-onset subtype.

BACKGROUND/AIMS: While DNA methylation and gastric microbiome are each associated with gastric cancer (GC), their combined role in predicting GC remains unclear. This study investigated the potential of a combined DNA methylation and gastric microbiome signature to predict Helicobacter pylori-negative GC. METHODS: In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of DKK3, SFRP1, EMX1, NKX6-1, MIR124-3, and TWIST1 in the gastric mucosa from 75 H. pylori-negative patients, including chronic gastritis (CG), intestinal metaplasia (IM), and GC. A combined analysis of DNA methylation and gastric microbiome, using 16S rRNA gene sequencing, was performed in 30 of 75 patients. RESULTS: The methylation levels of DKK3, SFRP1, EMX1, MIR124-3, and TWIST1 were significantly higher in patients with GC than in controls (all q

The clinical use of RNA interference (RNAi) molecular mechanisms has introduced a novel, growing class of RNA therapeutics capable of treating diseases by controlling target gene expression at the posttranscriptional level. With the newly approved nedosiran (Rivfloza), there are now six RNAi-based therapeutics approved by the United States Food and Drug Administration (FDA). Interestingly, five of the six FDA-approved small interfering RNA (siRNA) therapeutics [patisiran (Onpattro), lumasiran (Oxlumo), inclisiran (Leqvio), vutrisiran (Amvuttra), and nedosiran] were revealed to act on the 3'-untranslated regions of target mRNAs, instead of coding sequences, thereby following the common mechanistic action of genome-derived microRNAs (miRNA). Furthermore, three of the FDA-approved siRNA therapeutics [patisiran, givosiran (Givlaari), and nedosiran] induce target mRNA degradation or cleavage via near-complete rather than complete base-pair complementarity. These features along with previous findings confound the currently held characteristics to distinguish siRNAs and miRNAs or biosimilars, of which all converge in the RNAi regulatory pathway action. Herein, we discuss the RNAi mechanism of action and current criteria for distinguishing between miRNAs and siRNAs while summarizing the common and unique chemistry and molecular pharmacology of the six FDA-approved siRNA therapeutics. The term "RNAi" therapeutics, as used previously, provides a coherently unified nomenclature for broader RNAi forms as well as the growing number of therapeutic siRNAs and miRNAs or biosimilars that best aligns with current pharmacological nomenclature by mechanism of action. SIGNIFICANCE STATEMENT: The common and unique chemistry and molecular pharmacology of six FDA-approved siRNA therapeutics are summarized, in which nedosiran is newly approved. We point out rather a surprisingly mechanistic action as miRNAs for five siRNA therapeutics and discuss the differences and similarities between siRNAs and miRNAs that supports using a general and unified term "RNAi" therapeutics to align with current drug nomenclature criteria in pharmacology based on mechanism of action and embraces broader forms and growing number of novel RNAi therapeutics.

Synthetic biology constitutes a scientific domain focused on intentional redesign of organisms to confer novel functionalities or create new products through strategic engineering of their genetic makeup. Leveraging the inherent capabilities of nature, one may address challenges across diverse sectors including medicine. Inspired by this concept, we have developed an innovative bioengineering platform, enabling high-yield and large-scale production of biological small interfering RNA (BioRNA/siRNA) agents via bacterial fermentation. Herein, we show that with the use of a new tRNA fused pre-miRNA carrier, we can produce various forms of BioRNA/siRNA agents within living host cells. We report a high-level overexpression of nine target BioRNA/siRNA molecules at 100% success rate, yielding 3-10 mg of BioRNA/siRNA per 0.25 L of bacterial culture with high purity (>98%) and low endotoxin (

Because of their role in regulating and fine-tuning gene expression in the posttranscriptional period, microRNA (miRNA) may represent a mediating factor that connects diet and metabolic regulation. Given the vast number of miRNAs and that modulations in miRNA happen in response to a variety of stimuli, a comprehensive registry of miRNAs impacted by diet and the food items that modulate them, would have utility in the identification of miRNA complements for analysis of diet interventions and in helping to establish linkages between the specific impacts of diet components. A scoping literature search of online databases (PubMed, SCOPUS, EMBASE, and Web of Science) was performed. Only studies in human populations, those that used a diet intervention or meal challenge, and those that measured miRNA profiles in the same subject at multiple time points were included. Of the 6167 studies screened, only 25 met the study criteria and were included in the review. Seven studies examined miRNA following a meal challenge, whereas 18 investigated miRNA following a sustained diet intervention. The results demonstrated that miRNA are modulated following a variety of diet interventions and that intensity of miRNA response is greater in metabolically healthy subjects. Heterogeneity in the intensity and length of the diet intervention, the study populations being observed, and the methodology through which target miRNA are identified contribute to a lack of comparability across studies. The findings of this review highlight the need for more study of miRNA responsiveness to intake and provide recommendations for future research.

Genome-derived microRNAs (miRNAs or miRs) govern posttranscriptional gene regulation and play important roles in various cellular processes and disease progression. While chemo-engineered miRNA mimics or biosimilars made in vitro are widely available and used, miRNA agents produced in vivo are emerging to closely recapitulate natural miRNA species for research. Our recent work has demonstrated the success of high-yield, in vivo production of recombinant miRNAs by using human tRNA (htRNA) fused precursor miRNA (pre-miR) carriers. In this study, we aim to compare the production of bioengineered RNA (BioRNA) molecules with glycyl versus leucyl htRNA fused hsa-pre-miR-34a carriers, namely, BioRNAGly and BioRNALeu, respectively, and perform the initial functional assessment. We designed, cloned, overexpressed, and purified a total of 48 new BioRNA/miRNAs, and overall expression levels, final yields, and purities were revealed to be comparable between BioRNAGly and BioRNALeu molecules. Meanwhile, the two versions of BioRNA/miRNAs showed similar activities to inhibit non-small cell lung cancer cell viability. Interestingly, functional analyses using model BioRNA/miR-7-5p demonstrated that BioRNAGly/miR-7-5p exhibited greater efficiency to regulate a known target gene expression (EGFR) than BioRNALeu/miR-7-5p, consistent with miR-7-5p levels released in cells. Moreover, BioRNAGly/miR-7-5p showed comparable or slightly greater activities to modulate MRP1 and VDAC1 expression, compared with miRCURY LNA miR-7-5p mimic. Computational modeling illustrated overall comparable 3D structures for exemplary BioRNA/miRNAs with noticeable differences in htRNA species and payload miRNAs. These findings support the utility of hybrid htRNA/hsa-pre-miR-34a as reliable carriers for RNA molecular bioengineering, and the resultant BioRNAs serve as functional biologic RNAs for research and development.

Acute lung injury (ALI) is characterized by respiratory failure resulting from the disruption of the epithelial and endothelial barriers as well as immune system. In this study, we evaluated the therapeutic potential of airway epithelial cell-derived extracellular vesicles (EVs) in maintaining lung homeostasis. We isolated human bronchial epithelial cell-derived EVs (HBEC-EVs), which endogenously express various immune-related surface markers and investigated their immunomodulatory potential in ALI. In ALI cellular models, HBEC-EVs demonstrated immunosuppressive effects by reducing the secretion of proinflammatory cytokines in both THP-1 macrophages and HBECs. Mechanistically, these effects were partially ascribed to nine of the top 10 miRNAs enriched in HBEC-EVs, governing toll-like receptor-NF-κB signaling pathways. Proteomic analysis revealed the presence of proteins in HBEC-EVs involved in WNT and NF-κB signaling pathways, pivotal in inflammation regulation. ANXA1, a constituent of HBEC-EVs, interacts with formyl peptide receptor (FPR)2, eliciting anti-inflammatory responses by suppressing NF-κB signaling in inflamed epithelium, including type II alveolar epithelial cells. In a mouse model of ALI, intratracheal administration of HBEC-EVs reduced lung injury, inflammatory cell infiltration, and cytokine levels. Collectively, these findings suggest the therapeutic potential of HBEC-EVs, through their miRNAs and ANXA1 cargo, in mitigating lung injury and inflammation in ALI patients.

The obesity epidemic continues to worsen worldwide, driving metabolic and chronic inflammatory diseases. Thiazolidinediones, such as rosiglitazone (Rosi), are PPARγ agonists that promote 'M2-like' adipose tissue macrophage (ATM) polarization and cause insulin sensitization. As ATM-derived small extracellular vesicles (ATM-sEVs) from lean mice are known to increase insulin sensitivity, we assessed the metabolic effects of ATM-sEVs from Rosi-treated obese male mice (Rosi-ATM-sEVs). Here we show that Rosi leads to improved glucose and insulin tolerance, transcriptional repolarization of ATMs and increased sEV secretion. Administration of Rosi-ATM-sEVs rescues obesity-induced glucose intolerance and insulin sensitivity in vivo without the known thiazolidinedione-induced adverse effects of weight gain or haemodilution. Rosi-ATM-sEVs directly increase insulin sensitivity in adipocytes, myotubes and primary mouse and human hepatocytes. Additionally, we demonstrate that the miRNAs within Rosi-ATM-sEVs, primarily miR-690, are responsible for these beneficial metabolic effects. Thus, using ATM-sEVs with specific miRNAs may provide a therapeutic path to induce insulin sensitization.

Extracellular vesicles (EVs) play important roles in cell-cell communication but are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm with very limited amounts of cargos encapsulated. The technique of NanOstirBar (NOB)-EnabLed Single Particle Analysis (NOBEL-SPA) reported in the present work permits rapid inspection of single EV with high confidence by confocal fluorescence microscopy, thus enables colocalization assessment for selected protein and microRNA (miRNA) markers in the EVs produced by various cell lines, or present in clinical sera samples. EV subpopulations marked by the colocalization of unique protein and miRNA combinations were discovered to be able to detect early-stage (stage I or II) breast cancer (BC). NOBEL-SPA can be adapted to analyze other types of cargo molecules or other small submicron biological particles. Study of the sorting of specific cargos to heterogeneous vesicles under different physiological conditions can help discover distinct vesicle subpopulations valuable in clinical examination and therapeutics development and gain better understanding of their biogenesis.

Testicular germ cell tumors (TGCTs) are relatively common in young men, making accurate diagnosis and prognosis assessment essential. MicroRNAs (miRNAs), including microRNA-371a-3p (miR-371a-3p), have shown promise as biomarkers for TGCTs. This review discusses the recent advancements in the use of miRNA biomarkers in TGCTs, with a focus on the challenges surrounding the noninvasive detection of teratomas. Circulating miR-371a-3p, which is expressed in undifferentiated TGCTs but not in teratomas, is a promising biomarker for TGCTs. Its detection in serum, plasma, and, potentially, cystic fluid could be useful for TGCT diagnosis, surveillance, and monitoring of therapeutic response. Other miRNAs, such as miR-375-3p and miR-375-5p, have been investigated to differentiate between TGCT subtypes (teratoma, necrosis/fibrosis, and viable tumors), which can aid in treatment decisions. However, a reliable marker for teratoma has yet to be identified. The clinical applications of miRNA biomarkers could spare patients from unnecessary surgeries and allow for more personalized therapeutic approaches. Particularly in patients with residual masses larger than 1 cm following chemotherapy, it is critical to differentiate between viable tumors, teratomas, and necrosis/fibrosis. Teratomas, which mimic somatic tissues, present a challenge in differentiation and require a comprehensive diagnostic approach. The combination of miR-371 and miR-375 shows potential in enhancing diagnostic precision, aiding in distinguishing between teratomas, viable tumors, and necrosis. The implementation of miRNA biomarkers in TGCT care could improve patient outcomes, reduce overtreatment, and facilitate personalized therapeutic strategies. However, a reliable marker for teratoma is still lacking. Future research should focus on the clinical validation and standardization of these biomarkers to fully realize their potential.

BACKGROUND: Diabetes is a spectrum of metabolic diseases affecting millions of people worldwide. The loss of pancreatic β-cell mass by either autoimmune destruction or apoptosis, in type 1-diabetes (T1D) and type 2-diabetes (T2D), respectively, represents a pathophysiological process leading to insulin deficiency. Therefore, therapeutic strategies focusing on restoring β-cell mass and β-cell insulin secretory capacity may impact disease management. This study took advantage of powerful integrative bioinformatic tools to scrutinize publicly available diabetes-associated gene expression data to unveil novel potential molecular targets associated with β-cell dysfunction. METHODS: A comprehensive literature search for human studies on gene expression alterations in the pancreas associated with T1D and T2D was performed. A total of 6 studies were selected for data extraction and for bioinformatic analysis. Pathway enrichment analyses of differentially expressed genes (DEGs) were conducted, together with protein-protein interaction networks and the identification of potential transcription factors (TFs). For noncoding differentially expressed RNAs, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which exert regulatory activities associated with diabetes, identifying target genes and pathways regulated by these RNAs is fundamental for establishing a robust regulatory network. RESULTS: Comparisons of DEGs among the 6 studies showed 59 genes in common among 4 or more studies. Besides alterations in mRNA, it was possible to identify differentially expressed miRNA and lncRNA. Among the top transcription factors (TFs), HIPK2, KLF5, STAT1 and STAT3 emerged as potential regulators of the altered gene expression. Integrated analysis of protein-coding genes, miRNAs, and lncRNAs pointed out several pathways involved in metabolism, cell signaling, the immune system, cell adhesion, and interactions. Interestingly, the GABAergic synapse pathway emerged as the only common pathway to all datasets. CONCLUSIONS: This study demonstrated the power of bioinformatics tools in scrutinizing publicly available gene expression data, thereby revealing potential therapeutic targets like the GABAergic synapse pathway, which holds promise in modulating α-cells transdifferentiation into β-cells.

The Diabetes Prevention Program (DPP) randomized controlled trial demonstrated that metformin treatment reduced progression to type 2 diabetes (T2D) by 31% compared to placebo in adults with prediabetes. Circulating micro-ribonucleic acids (miRs) are promising biomarkers of T2D risk, but little is known about their associations with metformin regimens for T2D risk reduction. We compared the change in 24 circulating miRs from baseline to 2 years in a subset from DPP metformin intervention (n = 50) and placebo (n = 50) groups using Wilcoxon signed rank tests. Spearman correlations were used to evaluate associations between miR change and baseline clinical characteristics. Multiple linear regression was used to adjust for covariates. The sample was 73% female, 17% Black, 13% Hispanic, and 50 ± 11 years. Participants were obese, normotensive, prediabetic, and dyslipidemic. Change in 12 miR levels from baseline to 2 years was significantly different in the metformin group compared with placebo after adjusting for multiple comparisons: six (let-7c-5p, miR-151a-3p, miR-17-5p, miR-20b-5p, miR-29b-3p, and miR-93-5p) were significantly upregulated and six (miR-130b-3p, miR-22-3p, miR-222-3p, miR-320a-3p, miR-320c, miR-92a-3p) were significantly downregulated in the metformin group. These miRs help to explain how metformin is linked to T2D risk reduction, which may lead to novel biomarkers, therapeutics, and precision health strategies.

Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron-astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.

Recently, the siRNAs pathways, and especially reproductive phasiRNAs, have attracted attention in eudicots since their biological roles are still unknown and their biogenesis took different evolutionary pathways compared to monocots. In this work, we used Coffea arabica L., a recent allotetraploid formed from the hybridization of Coffea canephora and C. eugenioides unreduced gametes, to explore microsporogenesis and small RNAs-related pathways in a eudicot crop. First, we identified the microsporogenesis stages during anther development revealing that pre-meiosis occurs in anthers of 1.5 mm inside floral buds (FBs), whereas meiosis between 1.5 and 4.2 mm FBs, and post-meiosis in FBs larger than 4.2 mm. These stages coincide with the Brazilian winter, a period of FBs reduced growth which suggests temperature sensitivity. Next, we identified and quantified the expression of reproductive 21- and 24-nt phasiRNAs during coffee anther development together with their canonical and novel miRNA triggers, and characterized the DCL and AGO families. Our results showed that the pattern of reproductive phasiRNA abundance in C. arabica is unique among described eudicots and the canonical trigger car-miR2275 is involved in the processing of both 21- and 24-nt phasiRNAs. Fourteen DCL genes were identified, but DCL5, related to phasiRNA biosynthesis in monocots, was not, according to its specificity for monocots. Thus, our work explored the knowledge gap about microsporogenesis and related siRNAs pathways in coffee, contributing to the control of reproductive development and the improvement of fertility in eudicots.

Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

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

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

Background: MicroRNAs can regulate various biological functions including cell proliferation, differentiation, embryo formation, and implantation. The giant panda exhibits embryonic diapause, with embryo development resuming in late pregnancy. However, the changes in microRNAs during late pregnancy remain poorly understand. Methods and results: After mating, plasma samples were collected on day 40 of early pregnancy (EP; n = 3) and 30 days before delivery of late pregnancy (LP; n = 3). Following microRNAs screening, a total of 120 microRNAs were detected in the plasma exosomes of pregnant pandas. Nine differentially expressed microRNAs (DEmicroRNAs) were identified in LP compared to EP, including three that were upregulated and six that were downregulated. Notably, miR-25b and miR-47 were significantly downregulated in LP group. All DEmicroRNAs were predicted to target a total of 2,675 genes. Pathway enrichment analysis of these target genes revealed significant enrichment in the MAPK and Rap1 signaling pathways, which are closely related to cell proliferation, differentiation, and cell-cell and cell-matrix interactions. Analysis of protein-protein interaction networks showed that most of the hub genes (five out of eight), including Fgfr1, Fgf2, Fgf18, Erbb4, and Kras within the MAPK and Rap1 pathways are associated with the cell proliferation and differentiation. Significantly, Erbb4 was regulated by significantly differentially expressed miRNA-47. Conclusions: We suggest that plasma exosomal microRNAs are involved in cell proliferation and differentiation during embryonic development by regulating key hub genes within MAPK and Rap1 pathways. These findings provided new insights into the development of giant panda embryos. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has created a global pandemic with significant morbidity and mortality. SARS-CoV-2 primarily infects the lungs and is associated with various organ complications. Therapeutic approaches to combat COVID-19, including convalescent plasma and vaccination, have been developed. However, the high mutation rate of SARS-CoV-2 and its ability to inhibit host T-cell activity pose challenges for effective treatment. Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSCs–EVs) have shown promise in COVID-19 therapy because of their immunomodulatory and regenerative properties. MicroRNAs (miRNAs) play crucial regulatory roles in various biological processes and can be manipulated for therapeutic purposes. Objective: We aimed to investigate the role of lyophilized MSC–EVs and their microRNAs in targeting the receptors involved in SARS-CoV-2 entry into host cells as a strategy to limit infection. In silico microRNA prediction, structural predictions of the microRNA–mRNA duplex, and molecular docking with the Argonaut protein were performed. Methods: Male Syrian hamsters infected with SARS-CoV-2 were treated with human Wharton's jelly-derived Mesenchymal Stem cell-derived lyophilized exosomes (Bioluga Company)via intraperitoneal injection, and viral shedding was assessed. The potential therapeutic effects of MSCs–EVs were measured via histopathology of lung tissues and PCR for microRNAs. Results: The results revealed strong binding potential between miRNA‒mRNA duplexes and the AGO protein via molecular docking. MSCs–EVs reduced inflammation markers and normalized blood indices via the suppression of viral entry by regulating ACE2 and TMPRSS2 expression. MSCs–EVs alleviated histopathological aberrations. They improved lung histology and reduced collagen fiber deposition in infected lungs. Conclusion: We demonstrated that MSCs–EVs are a potential therapeutic option for treating COVID-19 by preventing viral entry into host cells. [ABSTRACT FROM AUTHOR]

Background Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from patients with severe COVID-19 vs controls, identifying potential mortality predictors. Methods This prospective study included 36 patients with severe COVID-19 and 33 controls without COVID-19. EV-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of patients with severe COVID-19 (n = 32) and controls (n = 12) was used to compare with our data. Survival analysis identified potential mortality predictors among the significantly differentially expressed (SDE) miRNAs in EVs. Results Patients with severe COVID-19 showed 50 SDE miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EV miRNAs were SDE in the plasma of severe cases vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an area under the receiver operating characteristic curve of 0.938. Conclusions This research provides insights into the role of miRNAs within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality. [ABSTRACT FROM AUTHOR]

Background: Curcumin is a polyphenol compound with anticancer effects. We aimed to review the anti‐neoplastic effects of curcumin on urogenital cancers, by regulating different microRNA expressions. Methods: A systematic search was conducted in Medline (PubMed), Embase, Scopus, and Web of Science up to the end of August 2024. All English, in vitro, and observational studies that evaluated the effect of curcumin on preventing or treating urogenital cancers through its impact on microRNA expression were included. In vivo or silico studies were excluded. Result: A total of 2549 records were found. Finally, 25 studies were included. Twelve studies assessed the effect of curcumin on prostate cancer, six studies on ovarian cancer, three studies on cervical cancer, three studies on bladder cancer, and one study on renal cancer. MicroRNAs are small noncoding RNAs that regulate the post‐transcriptional pathways. They possess pivotal roles in different fundamental mechanisms in cells such as differentiation, migration, apoptosis, and proliferation. Curcumin exerts its anticancer effects on urogenital neoplasms by upregulating tumor suppressor microRNAs (miR‐143, miR‐145, miR‐Let‐7, miR‐101, miR‐3127, miR‐3178, miR‐1275, miR‐3198, miR‐1908, miR‐770, miR‐1247, miR‐411, miR‐34a, miR‐383, miR‐708, miR‐483, miR‐199a, miR‐335, miR‐503, miR‐10b, miR‐551a, miR‐9, miR‐203, miR‐7110, miR‐29b, and miR‐126) and downregulating oncogenic microRNAs (miR‐21, miR‐210, miR‐382, miR‐654, miR‐494, miR‐193b, miR‐671, miR‐222, miR‐23b, miR‐664, miR‐183, miR‐214, miR‐320a, miR‐23a, miR‐30a, miR‐320d, miR‐1285, miR‐32, miR‐181a, miR‐205, miR‐216a, miR‐1246, and miR‐106b). Conclusion: Cell proliferation is inhibited, and cell apoptosis is induced by curcumin in different urogenital cancers through suppressing oncogenic microRNAs or provoking tumor suppressor microRNAs. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a progressive and catastrophic neurodegenerative disorder due to persistent infection with the aberrant measles virus in the brain. The exact etiology of SSPE is still unknown, and early diagnosis remains a challenge, especially with the atypical presentations. The pathogenesis of SSPE involves a complex interplay between viral factors and immunological response of the host. The presenting review demonstrates an extensive glimpse of the immuno‐genetics of SSPE, exploring the single‐nucleotide polymorphisms (SNPs), genetic risk factors and immune responses that influence susceptibility and disease progression. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. Recent research has emphasized a significant correlation between microRNAs (miRNAs) and PD. To identify key research areas, provide a comprehensive overview of current research in various fields, and propose potential directions for future studies, a bibliometric analysis was conducted on the involvement of miRNAs in Parkinson's disease from 2014 to 2023. Methods: Relevant literature records were collected from the Web of Science Core Collection on February 29, 2024. Subsequently, the data underwent analysis using the Bibliometrix R package and VOSviewer (version 1.6.19). Results: The annual scientific publications on miRNAs and Parkinson's disease demonstrated an increasing trend, with an annual growth rate of 12.67%. China, the United States, and India emerged as the top three most productive countries/regions. The University of Barcelona had the highest annual publications, followed by Central South University and the Helmholtz Association. The INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES held the top position in terms of H-index and total citations, reflecting its extensive influence and prolific publication output. Kim, J., Junn, E., Hébert, S.S., and Doxakis, E. were the most frequently co-cited authors in the field. Based on the analysis of keywords, the most frequently occurring terms included "alpha-synuclein," "neurodegenerative disease," "exosome," "neuroinflammation," "oxidative stress," "autophagy," and "amyotrophic lateral sclerosis," which have emerged as prominent research topics. Concurrently, there has been notable interest in topics such as "ceRNA," "lncRNAs," "mitochondrial dysfunction," and "circular RNA." Conclusion: This study focused on identifying emerging trends and critical research topics in the bibliometric analysis of microRNAs related to Parkinson's disease. These findings highlight the diverse research landscape and evolving trend of miRNA-related research in PD. The field of miRNA research in Parkinson's disease is actively exploring the underlying mechanisms of miRNA function, identifying potential diagnostic markers, and developing innovative therapeutic strategies. The results of our study offer significant contributions to researchers' ability to track contemporary developments and guide the trajectory of future research in this domain. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR‐1307‐3p is upregulated in BC tumors, yet its target genes are not fully elucidated. This study aimed to explore how miR‐1307‐3p regulates BC proliferation, migration, invasion, and angiogenesis and to identify potential target genes.Basal miR‐1307‐3p levels were quantified in BC cell lines MDA‐MB‐231 and MCF‐7, as well as MCF‐10A using quantitative real‐time reverse transcription‐PCR (RT‐qPCR). The impact of miR‐1307‐3p inhibition on BC cell proliferation, migration, invasion, and angiogenesis was assessed. Nine miRNA‐target prediction databases identified potential miR‐1307‐3p targets. Target expression was validated using RT‐qPCR, Western blot, and dual‐luciferase reporter assays. MiR‐1307‐3p was overexpressed in MDA‐MB‐231 and MCF‐7 compared to MCF‐10A.Inhibiting miR‐1307‐3p significantly reduced BC cell proliferation, migration, invasion, and angiogenesis. Bioinformatics analysis identified 17 potential miR‐1307‐3p targets, with protamine 2 (PRM2) overexpression confirmed via Western blot and dual‐luciferase assays.MiR‐1307‐3p overexpression in BC promotes proliferation, migration, invasion, and angiogenesis. PRM2 emerges as a novel miR‐1307‐3p target in BC. [ABSTRACT FROM AUTHOR]

DNA demethylases TET2 and TET3 play a fundamental role in thymic invariant natural killer T (iNKT) cell differentiation by mediating DNA demethylation of genes encoding for lineage specifying factors. Paradoxically, differential gene expression analysis revealed that significant number of genes were upregulated upon TET2 and TET3 loss in iNKT cells. This unexpected finding could be potentially explained if loss of TET proteins was reducing the expression of proteins that suppress gene expression. In this study, we discover that TET2 and TET3 synergistically regulate Drosha expression, by generating 5hmC across the gene body and by impacting chromatin accessibility. As DROSHA is involved in microRNA biogenesis, we proceed to investigate the impact of TET2/3 loss on microRNAs in iNKT cells. We report that among the downregulated microRNAs are members of the Let-7 family that downregulate in vivo the expression of the iNKT cell lineage specifying factor PLZF. Our data link TET proteins with microRNA expression and reveal an additional layer of TET mediated regulation of gene expression. [ABSTRACT FROM AUTHOR]

Background: Oral lichen planus (OLP) is a chronic inflammatory condition that can impact patients' quality of life. While its exact etiology remains unclear, it is associated with an increased risk of malignant transformation. Currently, the diagnosis of OLP relies on clinical examination and histopathological analysis, which can be invasive. Therefore, there is an urgent need for non-invasive and accurate diagnostic biomarkers. This systematic review and meta-analysis aims to investigate the potential of salivary microRNAs as promising candidates for OLP diagnosis. This meta-analysis seeks to identify specific microRNAs that are differentially expressed and could serve as reliable biomarkers for OLP diagnosis. Methods: Our strategy involved searching for pertinent keywords in multiple academic databases including Cochrane Library, Embase, LIVIVO, MEDLINE, Ovid, ProQuest, Scopus, Web of Science, Espacenet, and Google Scholar search engine. Upon identification, articles were screened and data extracted from the eligible studies. Split component synthesis method was utilized to assess specificity, sensitivity, likelihood and diagnostic odds ratios. The random-effects meta-analysis approach was used to combine study findings and develop pooled diagnostic performance metrics. Hierarchical summary receiver operating characteristic (ROC) plots were generated to determine area under the curve. Subgroup analyses concerning the type of saliva and control groups were also performed. Results: Among the fourteen studies included in our systematic review, five were eligible for meta-analysis. Salivary microRNAs showed the pooled sensitivity of 0.80 (95% Confidence Interval (95% CI): 0.68–0.88), specificity of 0.89 (95% CI: 0.82–0.94), diagnostic odds ratio of 28.45 (95% CI: 10.40–77.80), and area under the curve (AUC) of 0.93 for OLP diagnosis. Unstimulated saliva had higher sensitivity and specificity than oral swirl samples as the biomarker medium for OLP diagnosis. Meta-analysis uncovered that miR-27a, miR-137, miR-1290, miR-27b, miR-4484, miR-142, and miR-1246 had the highest diagnostic odds ratio for OLP. Conclusions: Our systematic review and meta-analysis demonstrate that salivary microRNAs can serve as valuable biomarkers for the diagnosis of OLP. The findings highlight the exceptional accuracy of salivary microRNAs in differentiating OLP patients from healthy controls and assessing the risk of malignant transformation. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small, non-coding RNAs that control gene expression by degrading or repressing mRNA translation into proteins. Research recently suggested that food-derived miRNAs are bioavailable and may be absorbed in the gastrointestinal tract (GIT). Since these small RNAs may reach the circulation and organs, possible interactions with host genes will lead to epigenetic effects that alter metabolism. Therefore, from a precision nutrition standpoint, exogenous miRNAs may be essential in modulating health status. This review summarizes the process of miRNA biogenesis, the post-translational mechanisms of gene regulation, and their bioavailability in animal- and plant-derived foods. [ABSTRACT FROM AUTHOR]

Apelin, a bioactive peptide that serves as an endogenous ligand for the apelin receptor (APJ), is overexpressed in various types of cancers and contributes to cancer cell proliferation, viability, migration, angiogenesis, and metastasis, as well as immune deviation. Noncoding RNAs (ncRNAs) regulate gene expression, and there is growing evidence suggesting a bidirectional crosstalk between ncRNAs (including long noncoding RNAs [lncRNAs], circular RNAs [circRNAs], and microRNAs [miRNAs]) and apelin in cancers. Certain miRNAs can directly target the apelin and inhibit its expression, thereby suppressing tumor growth. It has been indicated that miR‐224, miR‐195/miR‐195‐5p, miR‐204‐5p, miR‐631, miR‐4286, miR‐637, miR‐4493, and miR‐214‐3p target apelin mRNA and influence its expression in prostate cancer, lung cancer, esophageal cancer, chondrosarcoma, melanoma, gastric cancer, glioma, and hepatocellular carcinoma (HCC), respectively. Moreover, circ‐NOTCH1, circ‐ZNF264, and lncRNA BACE1‐AS upregulate apelin expression in gastric cancer, glioma, and HCC, respectively. On the other hand, apelin has been shown to regulate the expression of certain ncRNAs to affect tumorigenesis. It was revealed that apelin affects the expression of circ_0000004/miR‐1303, miR‐15a‐5p, and miR‐106a‐5p in osteosarcoma, lung cancer, and prostate cancer, respectively. This review explains a bidirectional interplay between ncRNAs and apelin in cancers to provide insights concerning the molecular mechanisms underlying this crosstalk and potential implications for cancer therapy. Significance: This manuscript highlights the critical role of apelin, a bioactive peptide, in various cancers and its interplay with ncRNAs. Understanding the bidirectional crosstalk between apelin and ncRNAs, including lncRNAs, circRNAs, and miRNAs, is pivotal for uncovering the molecular mechanisms underlying cancer progression. The identification of specific miRNAs and ncRNAs that target or regulate apelin in different cancers opens new avenues for therapeutic interventions. This review offers significant insights into how targeting the apelin‐ncRNA axis could potentially lead to innovative cancer treatments. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNA) are endogenously produced small, non-coded, single-stranded RNAs. Due to their involvement in various cellular processes and cross-communication with extracellular components, miRNAs are often coined the "grand managers" of the cell. miRNAs are frequently involved in upregulation as well as downregulation of specific gene expression and thus, are often found to play a vital role in the pathogenesis of multiple diseases. Central nervous system (CNS) diseases prove fatal due to the intricate nature of both their development and the methods used for treatment. A considerable amount of ongoing research aims to delineate the complex relationships between miRNAs and different diseases, including each of the neurological disorders discussed in the present review. Ongoing research suggests that specific miRNAs can play either a pathologic or restorative and/or protective role in various CNS diseases. Understanding how these miRNAs are involved in various regulatory processes of CNS such as neuroinflammation, neurovasculature, immune response, blood-brain barrier (BBB) integrity and angiogenesis is of empirical importance for developing effective therapies. Here in this review, we summarized the current state of knowledge of miRNAs and their roles in CNS diseases along with a focus on their association with neuroinflammation, innate immunity, neurovascular function and BBB. [ABSTRACT FROM AUTHOR]

Background: Immune stressors, such as lipopolysaccharides (LPS), profoundly affect microbiota balance, leading to gut dysbiosis. This imbalance disrupts the metabolic phenotype and structural integrity of the gut, increasing intestinal permeability. During puberty, a critical surge in estrogen levels is crucial for mammary gland development. However, inflammation originating from the gut in this period may interfere with this development, potentially heightening breast cancer risk later. The long‐term effects of pubertal inflammation on mammary development and breast cancer risk are underexplored. Such episodes can dysregulate cytokine levels and microRNA expression, altering mammary cell gene expression, and predisposing them to tumorigenesis. Methods: This study hypothesizes that prebiotics, specifically Lentinula edodes Cultured Extract (AHCC), can counteract LPS's adverse effects. Using BALB/c mice, an acute LPS dose was administered at puberty, and breast cancer predisposition was assessed at 13 weeks. Cytokine and tumor‐related microRNA levels, tumor development, and cancer stem cells were explored through immunoassays and qRT‐PCR. Results: Results show that LPS induces lasting effects on cytokine and microRNA expression in mammary glands and tumors. AHCC modulates cytokine expression, including IL‐1β, IL‐17A/F, and IL‐23, and mitigates LPS‐induced IL‐6 in mammary glands. It also regulates microRNA expression linked to tumor progression and suppression, particularly counteracting the upregulation of oncogenic miR‐21, miR‐92, and miR‐155. Although AHCC slightly alters some tumor‐suppressive microRNAs, these changes are modest, highlighting a complex regulatory role that warrants further study. Conclusion: These findings underscore the potential of dietary interventions like AHCC to mitigate pubertal LPS‐induced inflammation on mammary gland development and tumor formation, suggesting a preventive strategy against breast cancer. [ABSTRACT FROM AUTHOR]

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

Cachexia is a late consequence of various diseases that is characterized by systemic muscle loss, with or without fat loss, leading to significant mortality. Multiple signaling pathways and molecules that increase catabolism, decrease anabolism, and interfere with muscle regeneration are activated. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play vital roles in cachexia muscle atrophy. This review mainly provides the mechanisms of specific ncRNAs to regulate muscle loss during cachexia and discusses the role of ncRNAs in cachectic biomarkers and novel therapeutic strategies that could offer new insights for clinical practice. [ABSTRACT FROM AUTHOR]

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

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

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

Brain metastasis is a significant clinical challenge for patients with advanced lung cancer, occurring in about 20–40% of cases. Brain metastasis causes severe neurological symptoms, leading to a poor prognosis and contributing significantly to lung cancer-related mortality. However, the underlying molecular mechanism behind brain metastasis remains largely unknown. MicroRNAs (miRNAs) are small, non-coding RNAs linked to several aspects of cancer progression, including metastasis. In the context of lung cancer, significant research has shown the involvement of miRNAs in regulating critical pathways related to metastatic spread to the brain. This review summarizes the scientific evidence regarding the regulatory roles of intra- and extracellular miRNAs, which specifically drive the spread of lung cancer cells to the brain. It also revises the known molecular mechanisms of brain metastasis, focusing on those from lung cancer as the primary tumor to better understand the complex mechanisms underlying this regulation. Understanding these complex regulatory mechanisms holds promise for developing novel diagnostic biomarkers and potential therapeutic strategies in brain metastasis. [ABSTRACT FROM AUTHOR]

Aims: This study aims to investigate miR‐486‐5p and miR‐novel‐chr1_40444 expressions in dysglycemic individuals. Validating RNA‐sequencing findings in a larger sample via reverse transcription qPCR (RT‐qPCR), we aim to address global diagnostic and screening limitations, using an African cohort as an example. Materials and Methods: This cross‐sectional study involved 1,271 individuals [normoglycemic (n = 974), prediabetic (n = 206), screen‐detected type 2 diabetes (n = 91)] from the ongoing Vascular and Metabolic Health (VMH) study in Cape Town, South Africa. Whole blood miRNA expression was assessed using TaqMan‐based RT‐qPCR, with data normalized to an endogenous control (miR‐16‐5p). Results: Significant underexpression was observed in prediabetes vs normoglycemia for miR‐486‐5p (P = 0.038), whilst both miRNAs demonstrated significant upregulation in screen‐detected type 2 diabetes vs normoglycemia (miR‐486‐5p, P = 0.009; miR‐novel‐chr1_40444, P < 0.001), and screen‐detected type 2 diabetes in comparison with prediabetes (miR‐486‐5p, P < 0.001; miR‐novel‐chr1_40444, P < 0.001). Multivariable regression analyses revealed pronounced interrelations between miR‐novel‐chr1_40444 and screen‐detected type 2 diabetes in unadjusted and adjusted models (Model 1: P < 0.001, Model 2: P < 0.001, Model 3: P = 0.030). Moreover, receiver operating characteristic (ROC) curves revealed significantly enhanced diagnostic capabilities for screen‐detected type 2 diabetes vs either normoglycemia (AUC = 0.971, P < 0.001), non‐diabetes (AUC = 0.959, P < 0.001), or prediabetes (AUC = 0.902, P < 0.001) when combining the miRNAs with 2 h postprandial glucose. Conclusions: This study demonstrated the enhanced power of incorporating miRNAs with traditional markers in distinguishing screen‐detected type 2 diabetes, warranting further investigations on their unique role in the development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

• Transcriptomic analyses revealed the activation of inflammatory-related pathways in VULN rats. • Transcriptomic analyses revealed the inhibition of pathways involved in protein synthesis in VULN rats. • Transcriptomic analyses suggested the activation of pathways involved in neurotransmission in RES rats. • Most significant mRNA-miRNA pairs were involved in inflammation and in the olfactory sensory system in VULN rats. Stress is a major risk factor for the development of psychiatric disorders, including depression. However, its effects are not the same in all the subjects as only a portion of individuals exposed to stress will eventually develop negative mental outcomes, while others can be considered resilient. However, the biological processes underlying the development of a vulnerable or resilient phenotype are still poor understood. In order to cover this, we here used both transcriptomic and miRNomic based approaches in the ventral hippocampus of control (CON) and rats exposed to the chronic mild stress (CMS) paradigm, which were then divided into vulnerable (VULN) or resilient (RES) animals according to the sucrose consumption test. Transcriptomic analyses in VULN rats, compared to both the group of CON and RES animals, revealed the activation of inflammatory/immune-related pathways, specifically involved in antibodies and cytokine production, and the inhibition of pathways involved in protein synthesis. Conversely, transcriptomic data in RES animals suggested the activation of several pathways involved in neurotransmission. We then performed a mRNA-miRNA integration analysis by using miRComb R package, and we found that the most significant mRNA-miRNA pairs were involved in promoting the inflammatory status in VULN animals and, vice versa, by decreasing it in RES rats. Moreover, in VULN animals, the mRNA-miRNA combining analyses revealed the modulation of the olfactory sensory system, a key biological process that has been already found involved in the etiology of stress related disorders such as depression. Overall, our mRNA-miRNA integration-based approach identified distinct biological processes that are relevant for the development of a vulnerable or resilient phenotype in response to the negative effects of CMS exposure, which could allow the identification of novel targets for prevention or treatment. [ABSTRACT FROM AUTHOR]

Tooth development, or odontogenesis, is a complex process in which several molecular pathways play a key role. Recently, microRNAs, a class of approximately 20-nucleotide small RNA molecules that regulate gene expression, have been implicated in the odontogenesis process. This study aimed to assess the role of miRNAs in odontogenesis anomalies, specifically agenesis and impaction. We analyzed a manually curated list of 82 miRNAs associated with human odontogenesis, sourced from literature data. Employing two different approaches to validate findings, we conducted functional enrichment analysis to evaluate the cell pathways, diseases, and phenotypes enriched for those miRNAs. Our findings indicate that the analyzed miRNAs regulate pathways linked to tooth anomalies, including the TGFꞵ and Wnt signaling pathways, and those governing the pluripotency of stem cells, known to mediate various cellular processes, and interconnected with odontogenesis-related pathways. Furthermore, the analysis disclosed several pathways associated with tumors, including small cell lung and gastric cancer. These results were confirmed also by diseases and phenotypes enrichment evaluation. Moreover, cell network analysis disclosed that miRNAs are embedded and interconnected in networks associated with dental diseases and cancer development, thus confirming the functional enrichment analyses. In summary, our results offer a quantitative measure of the potential involvement of miRNAs in regulating pathways crucial for developmental processes, notably odontogenesis, and provide results suggesting potential association with oncogenesis processes as well. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine the target genes of upregulated miRNAs in endometriosis. Methods: In this study, 18 controls, 18 eutopic and 18 ectopic samples were analysed. Profiling and validation of miRNAs associated with functions of endometriosis were performed using next-generation sequencing (NGS) and qRT-PCR. At the same time, the expression of ERα, ERβ, PR-A and PR-B was also determined using qRT-PCR. Target prediction was also performed for miR-199a-3p, miR-1-3p and miR-125b-5p using StarBase. Results: In this study, NGS identified seven significantly differentially expressed miRNAs, of which six miRNAs related to the role of endometriosis were selected for validation by qRT-PCR. The expression of miR-199a-3p, miR-1-3p, miR-146a-5p and miR-125b-5p was upregulated in the ectopic group compared to the eutopic group. Meanwhile, ERα and ERβ were significantly differentially expressed in endometriosis compared to the control group. However, the expressions of PR-A and PR-B showed no significant differences between the groups. The predicted target genes for miR-199a-3p, miR-1-3p and miR-125b-5p are SCD, TAOK1, DDIT4, LASP1, CDK6, TAGLN2, G6PD and ELOVL6. Conclusions: Our findings demonstrated that the expressions of ERα and ERβ might be regulated by miRNAs contributing to progesterone resistance, whereas the binding of miRNAs to target genes could also contribute to the pathogenesis of endometriosis. Therefore, miRNAs could be used as potential biomarkers and for targeted therapy in patients with endometriosis. [ABSTRACT FROM AUTHOR]

Environmental factors such as heavy metals can influence the gene expression profiles that can lead to diseases. MicroRNAs (miRNAs) are primary regulatory molecules related to health and disease that are sensitive to environmental factors. Several studies have shown an association between environmental exposure to toxic metals such as cadmium (Cd) and disease risk. Growing knowledge has shown that heavy metal toxicity can manifest through miRNAs. Therefore, dysregulated miRNAs are proposed as potential biomarkers for monitoring chronic metal exposure. This review aimed to evaluate the effect of Cd on changes in miRNA expression. The databases of PubMed, Web of Science (ISI), Scopus, and Google Scholar were systematically searched for all previous relevant articles from 2000 up to 2022. The following medical subject headings were used: (microRNAs OR miRs) AND (Heavy Metals OR Cadmium OR Cd) AND (miRs profile OR miRs Expression). Searched articles were divided into the categories of in vitro, in vivo, and human studies. MiRNAs, widely used for biomarker discovery in Cdinduced diseases, are still being researched to use these genes for reliable biomarker discovery in addition to current diagnostic and prognostic approaches. As the functional effects of miRNAs are by their target proteins, it is important to analyze the expression levels of multiple potential target proteins to fully understand the role and mechanism of miRNAs in Cd-induced diseases. Therefore, further investigations are required to understand the regulatory mechanisms of miRNAs and to obtain novel biomarkers, and these findings will be used to develop early diagnostic approaches as well as new preventive methods and treatment options for Cd-induced diseases. [ABSTRACT FROM AUTHOR]

Background an objectives: Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between "healthy" nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA (mRNA) metabolism, showcasing the power of our approach. Methods: To achieve this, we used: (a) infinite (finitely generated) groups, with generators representing the distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly(A) tail in item (ii), and the microRNA seed in item (iii)]; (b) aperiodicity theory, which connects healthy groups to free groups of rank r and their profinite completion, and (c) the representation theory of groups over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety. Results: We investigate (1) mRNA translation in prokaryotes and eukaryotes, (2) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (3) microRNAs involved in RNA silencing and posttranscriptional regulation of gene expression, and (4) identification of disrupted sequences that could lead to potential illnesses. Conclusion: Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies. [ABSTRACT FROM AUTHOR]

Since prostate cancer is one of the leading causes of cancer-related death, a better understanding of the molecular pathways guiding its development is imperative. A key factor in prostate cancer is autophagy, a cellular mechanism that affects both cell survival and death. Autophagy is essential in maintaining cellular homeostasis. Autophagy is a physiological mechanism wherein redundant or malfunctioning cellular constituents are broken down and recycled. It is essential for preserving cellular homeostasis and is implicated in several physiological and pathological conditions, including cancer. Autophagy has been linked to metastasis, tumor development, and treatment resistance in prostate cancer. The deregulation of miRNAs related to autophagy appears to be a crucial element in the etiology of prostate cancer. These miRNAs influence the destiny of cancer cells by finely regulating autophagic mechanisms. Numerous investigations have emphasized the dual function of specific miRNAs in prostate cancer, which alter autophagy-related pathways to function as either tumor suppressors or oncogenes. Notably, miRNAs have been linked to the control of autophagy and the proliferation, apoptosis, and migration of prostate cancer cells. To create customized therapy approaches, it is imperative to comprehend the dynamic interplay between autophagy and miRNAs in prostate cancer. The identification of key miRNAs provides potential diagnostic and prognostic markers. Unraveling the complex network of lncRNAs, like PCA3, also expands the repertoire of molecular targets for therapeutic interventions. This review explores the intricate interplay between autophagy and miRNAs in prostate cancer, focusing on their regulatory roles in cellular processes ranging from survival to programmed cell death. [ABSTRACT FROM AUTHOR]

Purpose of the Review: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle. Recent Findings: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Summary: Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3β activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia. [ABSTRACT FROM AUTHOR]

Oral premalignant disorders (OPMDs) are a group of potentially malignant conditions that pose a significant health burden globally. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as crucial regulators of gene expression and have been implicated in various biological processes, including carcinogenesis. This review synthesizes existing knowledge to provide a comprehensive understanding of the molecular mechanisms underlying OPMDs and to highlight the potential of miRNAs as promising biomarkers and therapeutic targets. Additionally, this review seeks to explore the potential of miRNA-based diagnostic biomarkers for early detection of OPMDs in the current literature on miRNAs in OPMDs, examining their involvement in disease pathogenesis, diagnostic potential, and therapeutic implications. Dysregulated miRNAs can target genes involved in critical cellular processes, such as cell cycle regulation, apoptosis, and DNA repair, leading to disease progression. Notably, miR-21, miR-31, miR-135b, and miR-486-5p have shown promise as potential biomarkers for early detection of oral premalignant lesions. Furthermore, the paper discusses the therapeutic implications of miRNAs in OPMDs. Preclinical studies have demonstrated the efficacy of miRNA-targeted therapies, such as miRNA mimics and inhibitors, in suppressing the growth of oral premalignant lesions. Early-phase clinical trials have shown promising results, indicating the potential for personalized treatment approaches. The findings underscore the importance of understanding the molecular mechanisms underlying these disorders and provide insights for the development of improved diagnostic and therapeutic strategies. However, they pose certain limitations given their intrinsic variability in expression profiles, the need for optimized isolation and detection methods, and potential hurdles in transitioning from preclinical success to clinical applications. Thus, future clinical studies are warranted to fully exploit the potential of miRNAs in the management of OPMDs. [ABSTRACT FROM AUTHOR]

Objectives: Non-coding RNA (ncRNA) plays a role in the development of diabetes and coronary heart disease. However, there is limited research on the association between ncRNA and these conditions. This study aims to conduct a bibliometric analysis and visualization of existing research to provide a comprehensive reference for future investigation in this field. Methods: We searched the China National Knowledge Infrastructure (CNKI) and Web of Science Core Collection (WoSCC) databases for articles published from 2012 to 2024. We analyzed publication volume, country of origin, authors, and keywords using Microsoft Office Excel, CiteSpace, and VOSviewer. Results: A total of 414 papers from 56 countries/regions, involving 298 authors, were analyzed. China had the highest number of publications (177), followed by the USA (90) and Italy (28). The number of publications generally shows an increasing trend. Collaborative research efforts were prevalent, with Katare Rajesh being the most cited author on average. International Journal of Molecular Sciences emerged as the most prolific journal in this field, while the article "MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart" was identified as the most frequently cited. The analysis of keywords and literature indicates that current research predominantly focuses on the expression and mechanisms of ncRNA in disease, as well as its potential as a biomarker. Conclusion: Research on ncRNA in the context of diabetes and coronary heart disease has made notable strides, although it warrants further exploration. Through bibliometric and visual analysis, we elucidate the collaborative relationships among researchers, which can facilitate the identification of potential collaborators. Additionally, we delineate the key areas and emergent trends in this field, providing valuable insights that can guide researchers in selecting future research directions. Plain Language Summary: Tables and pictures are used to show the research status of ncRNA in diabetes mellitus with coronary heart disease This research explores the connection between a type of RNA called ncRNA and two common diseases: diabetes and coronary heart disease. We used a method called bibliometrics to analyze over 400 research papers published on this topic from 2012 to 2024. What we found: • The number of studies on ncRNA and diabetes with heart disease has been increasing over the past 12 years, indicating growing interest in this area. • China and the United States have published the most research on this topic, but international collaboration could further enhance the impact of these studies. • Some scientists, like Rajesh Katare, have made significant contributions to this field with their research on miRNA as a potential biomarker for heart disease in diabetes patients. • The most common journals publishing research on this topic include the International Journal of Molecular Sciences and the Journal of the American College of Cardiology. • The main focus of current research is understanding how ncRNA is expressed and functions in these diseases, and its potential as a biomarker for early diagnosis and treatment. Why this is important: • Diabetes and coronary heart disease are major health problems worldwide, causing significant illness and death. • ncRNA has the potential to be used as a biomarker for these diseases, which could lead to earlier diagnosis and better treatment options. • Understanding the role of ncRNA in these diseases could also help develop new treatments that target the underlying causes of the diseases. What's next: • Future research should focus on understanding the role of long noncoding RNA in diabetes and heart disease, as this type of RNA is thought to be important in regulating genes related to these diseases. • Increased international collaboration could. help further advance the field and improve the impact of research findings. [ABSTRACT FROM AUTHOR]

Nuclear receptors (NRs) function as crucial transcription factors in orchestrating essential functions within the realms of development, host defense, and homeostasis of body. NRs have garnered increased attention due to their potential as therapeutic targets, with drugs directed at NRs demonstrating significant efficacy in impeding chronic disease progression. Consequently, these pharmacological agents hold promise for the treatment and management of various diseases. Accumulating evidence emphasizes the regulatory role of exosome-derived microRNAs (miRNAs) in chronic inflammation, disease progression, and therapy resistance, primarily by modulating transcription factors, particularly NRs. By exploiting inflammatory pathways such as protein kinase B (Akt)/mammalian target of rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and Wnt/β-catenin signaling, exosomes and NRs play a pivotal role in the panorama of development, physiology, and pathology. The internalization of exosomes modulates NRs and initiates diverse autocrine or paracrine signaling cascades, influencing various processes in recipient cells such as survival, proliferation, differentiation, metabolism, and cellular defense mechanisms. This comprehensive review meticulously examines the involvement of exosome-mediated NR regulation in the pathogenesis of chronic ailments, including atherosclerosis, cancer, diabetes, liver diseases, and respiratory conditions. Additionally, it elucidates the molecular intricacies of exosome-mediated communication between host and recipient cells via NRs, leading to immunomodulation. Furthermore, it outlines the implications of exosome-modulated NR pathways in the prophylaxis of chronic inflammation, delineates current limitations, and provides insights into future perspectives. This review also presents existing evidence on the role of exosomes and their components in the emergence of therapeutic resistance. [ABSTRACT FROM AUTHOR]

A burn is a type of injury to the skin or other tissues caused by heat, chemicals, electricity, sunlight, or radiation. Burn injuries have been proven to have the potential for long-term detrimental effects on the human body. The conventional therapeutic approaches are not able to effectively and easily heal these burn wounds completely. The main potential drawbacks of these treatments include hypertrophic scarring, contracture, infection, necrosis, allergic reactions, prolonged healing times, and unsatisfactory cosmetic results. The existence of these drawbacks and limitations in current treatment approaches necessitates the need to search for and develop better, more efficient therapies. The regenerative potential of microRNAs (miRNAs) and the exosomal miRNAs derived from various cell types, especially stem cells, offer advantages that outweigh traditional burn wound healing treatment procedures. The use of multiple types of stem cells is gaining interest due to their improved healing efficiency for various applications. Stem cells have several key distinguishing characteristics, including the ability to promote more effective and rapid healing of burn wounds, reduced inflammation levels at the wound site, and less scar tissue formation and fibrosis. In this review, we have discussed the stages of wound healing, the role of exosomes and miRNAs in improving thermal-induced wounds, and the impact of miRNAs in preventing the formation of hypertrophic scars. Research studies, pre-clinical and clinical, on the use of different cell-derived exosomal miRNAs and miRNAs for the treatment of thermal burns have been documented from the year 2000 up to the current time. Studies show that the use of different cell-derived exosomal miRNAs and miRNAs can improve the healing of burn wounds. The migration of exosomal miRNAs to the site of a wound leads to inhibition of apoptosis, induction of autophagy, re-epithelialization, granulation, regeneration of skin appendages, and angiogenesis. In conclusion, this study underscores the importance of integrating miRNA and exosome research into treatment strategies for burn injuries, paving the way for novel therapeutic approaches that could significantly improve patient outcomes and recovery times. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are potentially useful biomarkers for the evaluation of cancers and chemical toxicity. However, simply and easily operated detection techniques are increasingly needed to enable their use in the biomedical and environmental fields. In this study, we investigated sequence-specific miRNA detections by surface plasmon resonance (SPR) and electrochemical (EC) imaging measurements on SPR-EC chips possessing a Au electrode array modified with probe DNAs and by employing a miRNA-detection-selective signal amplification method. MiRNAs were sequence-specifically detected by SPR and EC imaging measurements on a single chip. SPR signals were enhanced by a combination process employing the sequencespecific hybridization of miRNAs with the probe DNA, the extension reaction of polyadenine [poly(A)] tails on the 3’ end of the miRNAs by poly(A) polymerase, the binding of T30-Au nanoparticles (AuNPs) to the poly(A) tails, and the reduction reaction of Ag+ catalyzed on the AuNPs, depositing a gray precipitate on the surface. The oxidation reaction of the accumulated Ag precipitation additionally provides EC signal amplification. This process considerably and sequence-specifically amplifies the SPR and EC signals. This setup constitutes a simple and feasible signal amplification method for the on-site detection of miRNA biomarkers. [ABSTRACT FROM AUTHOR]

Hemiptera is one of the most significant orders of insect pests, including whiteflies, true bugs, aphids, planthoppers, psyllids, and so forth, which have led to substantial economic losses in agricultural industries and have significantly affected food yields through their ability to suck the phloem sap of crops and transmit numerous bacterial and viral pathogens. Therefore, explorations of pest‐specific, eco‐friendly and easy‐to‐adopt technologies for hemipteran pest control are urgently needed. To the best of our knowledge, microRNAs (miRNAs), which are endogenous non‐coding small RNAs approximately 22 nucleotides in length, are involved in regulating gene expression via the direct recognition and binding of the 3′‐untranslated region (3′‐UTR) of target messenger RNAs (mRNAs) or by acting as a center of a competitive endogenous RNA (ceRNA) network at the post‐transcriptional level. This review systematically outlines the characterization and functional investigation of the miRNA biogenesis pathway in hemipteran pests, such as whiteflies, true bugs, aphids and planthoppers. In addition, we explored the results of small RNA sequencing and functional observations of miRNAs in these pests, and the results suggest that the numerous miRNAs obtained and annotated via high‐throughput sequencing technology and bioinformatic analyses contribute to molting development, fitness, wing polyphenism, symbiont interactions and insecticide resistance in hemipteran pests. Finally, we summarize current advances and propose a framework for future research to extend the current data and address potential limitations in the investigation and application of hemipteran miRNAs. [ABSTRACT FROM AUTHOR]