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Background Glioma is the second most common type of brain tumor, accounting for 24% of all brain tumor cases. The current diagnostic procedure is through an invasive tissue sampling to obtain histopathological analysis, however, not all patients are able to undergo a high-risk procedure. Circulating microRNAs (miRNAs) are considered as promising biomarkers for glioma due to their sensitivity, specificity, and non-invasive properties. There is currently no defined miRNA profile that contributes to determining the grade of glioma. This study aims to find the answer for “Is there any significant miRNA that able to distinguish different grades of glioma?”. Methods This study was conducted to compare the expression of miRNAs between low-grade glioma (LGG) and high-grade glioma (HGG). Eighteen blood plasma samples from glioma patients and 6 healthy controls were analyzed for 798 human miRNA profiles using NanoString nCounter Human v3 miRNA Expression Assay. The differential expressions of miRNAs were then analyzed to identify the differences in miRNA expression between LGG and HGG. Results Analyses showed significant expressions in 12 miRNAs between LGG and HGG, where all of them were downregulated. Out of these significant miRNAs, miR-518b, miR-1271-3p, and miR-598-3p showed the highest potential for distinguishing HGG from LGG, with area under curve (AUC) values of 0.912, 0.889, and 0.991, respectively. Conclusion miR-518b, miR-1271-3p, and miR-598-3p demonstrate significant potentials in distinguishing LGG and HGG.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic biomarkers. Since microRNAs (miRNAs) contribute to oncogenesis and metastasis formation in PDAC, they are considered potential candidates for fulfilling this task. In this work, the levels of two miRNA subsets (involved in chemoresistance or with oncogenic/tumor suppressing functions) were investigated in a panel of PDAC cell lines and liquid biopsies of a small cohort of patients. We used RT-qPCR and droplet digital PCR (ddPCR) to measure the amounts of cellular- and vesicle-associated, and circulating miRNAs. We found that both PDAC cell lines, also after gemcitabine treatment, and patients showed low amounts of cellular-and vesicle-associated miR-155-5p, compared to controls. Interestingly, we did not find any differences when we analyzed circulating miR-155-5p. Furthermore, vesicle-related miR-27a-3p increased in cancer patients compared to the controls, while circulating let-7a-5p, miR-221-3p, miR-23b-3p and miR-193a-3p presented as dysregulated in patients compared to healthy individuals. Our results highlight the potential clinical significance of these analyzed miRNAs as non-invasive diagnostic molecular tools to characterize PDAC. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD), with a prevalence of 30% of adults globally, is considered a multifactorial disease. There is a lack of effective non-invasive methods for accurate diagnosis and monitoring. Therefore, this study aimed to explore associations between changes in circulating miRNA levels, inflammatory markers, and depressive symptoms with hepatic variables in MASLD subjects and their combined potential to predict the disease after following a dietary intervention. Biochemical markers, body composition, circulating miRNAs and hepatic and psychological status of 55 subjects with MASLD with obesity and overweight from the FLiO study were evaluated by undergoing a 6-, 12- and 24-month nutritional intervention. The highest accuracy values of combined panels to predict the disease were identified after 24 months. A combination panel that included changes in liver stiffness, high-density lipoprotein cholesterol (HDL-c), body mass index (BMI), depressive symptoms, and triglycerides (TG) yielded an AUC of 0.90. Another panel that included changes in hepatic fat content, total cholesterol (TC), miR15b-3p, TG, and depressive symptoms revealed an AUC of 0.89. These findings identify non-invasive biomarker panels including circulating miRNAs, inflammatory markers, depressive symptoms and other metabolic variables for predicting MASLD presence and emphasize the importance of precision nutrition in MASLD management and the sustained adherence to healthy lifestyle patterns. [ABSTRACT FROM AUTHOR]

We recently derived and validated a serum‐based microRNA risk score (miR‐score) that predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow‐up in a population‐based cohort study from Germany (ESTHER cohort). Here, we aimed to evaluate associations of the CRC‐specific miR‐score with the risk of developing other common cancers, including female breast cancer (BC), lung cancer (LC), and prostate cancer (PC), in the ESTHER cohort. MicroRNAs (miRNAs) were profiled by quantitative real‐time PCR in serum samples collected at baseline from randomly selected incident cases of BC (n = 90), LC (n = 88), and PC (n = 93) and participants without diagnosis of CRC, LC, BC, or PC (controls, n = 181) until the end of the 17‐year follow‐up. Multivariate logistic regression models were used to evaluate the associations of the miR‐score with BC, LC, and PC incidence. The miR‐score showed strong inverse associations with BC and LC incidence [odds ratio per 1 standard deviation increase: 0.60 (95% confidence interval [CI] 0.43–0.82), p = 0.0017, and 0.64 (95% CI 0.48–0.84),p = 0.0015, respectively]. Associations with PC were not statistically significant but pointed in the positive direction. Our study highlights the potential of serum‐based miRNA biomarkers for cancer‐specific risk prediction. Further large cohort studies aiming to investigate, validate, and optimize the use of circulating miRNA signatures for cancer risk assessment are warranted. Circulating microRNAs (miRNAs) could improve cancer risk prediction. Our findings demonstrate that miRNA profiles associated with tumor progression differ across cancer types and could be useful for developing personalized cancer prevention strategies. [ABSTRACT FROM AUTHOR]

IntroductionThe preservation of locally endangered breeds is essential for maintaining ecosystem services that benefit both society and the environment. Reproductive fitness becomes a crucial consideration in this context. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a key role in post-transcriptional regulation. Typically, they function within the tissues where they are produced. However, when they are released into extracellular fluid, they are referred to as circulating miRNAs (c-miRNAs). C-miRNAs may serve as potential biomarkers, whose profile changes under different physiological states. The purpose of this study is to establish a connection between distinctive variations in the expression of c-miRNAs and specific estrus cycle phases in Frabosana-Roaschina sheep, an endangered Piedmontese breed.MethodsTwo trials, each involving 20 ewes with different reproductive efficiencies (nulliparous in the first trial and pluriparous in the second trial), were sampled on alternate days after synchronization for blood, saliva, and feces. Ultrasound scans were performed during the induced estrus cycle. The animals’ behaviors were assessed through video recordings.ResultsIn the first trial, play behaviors were detected without sexual behaviors, whereas in the second trial, sexual behaviors were observed without play behaviors. Based on plasma trends of 17β-estradiol and progesterone and ultrasound images, two moments were identified for miRNAs analyses: the beginning of the follicular phase (day 2) and the beginning of the luteal phase (day 11). C-miRNAs of six representative animals from the second trial were sequenced. Analyses of the sequencing data have identified 12 c-miRNAs that were differentially expressed (DE) when comparing day 11 with day 2: five miRNAs were found to be upregulated, whereas seven miRNAs were downregulated. An enrichment analysis, based on predicted targets, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases was performed. Many of these genes regulate reproductive pathways with the possible involvement of miRNAs. Finally, qRT-PCR was conducted to validate the DE miRNAs in all ewes. Differences in gene expression between the two sampling points and the two trials were observed, in line with existing literature.DiscussionInvestigating the role of these miRNAs in regulating estrus could improve the reproductive performance and welfare of Frabosana-Roaschina ewes.

Abstract Background Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. Methods We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). Results We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. Conclusions miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.

MicroRNAs (miRNAs) play a crucial role in the early diagnosis of autoinflammatory diseases, with Hidradenitis Suppurativa (HS) being a notable example. HS, an autoinflammatory skin disease affecting the pilosebaceous unit, profoundly impacts patients' quality of life. Its hidden nature, with insidious initial symptoms and patient reluctance to seek medical consultation, often leads to a diagnostic delay of up to 7 years. Recognizing the urgency for early diagnostic tools, recent research identified significant differences in circulating miRNA expression, including miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p, between HS patients and healthy controls. These miRNAs serve as potential biomarkers for earlier disease detection. Traditional molecular biology techniques, like reverse transcription quantitative-polymerase chain reaction (RT-qPCR), are employed for their detection using specific primers and probes. Alternatively, short peptides offer a versatile and effective means for capturing miRNAs, providing specificity, ease of synthesis, stability, and multiplexing potential. In this context, we present a computational simulation pipeline designed for crafting peptide sequences that can capture circulating miRNAs in the blood of patients with autoinflammatory skin diseases, including HS. This innovative approach aims to expedite early diagnosis and enhance therapeutic follow-up, addressing the critical need for timely intervention in HS and similar conditions. [ABSTRACT FROM AUTHOR]

Micro-ribonucleic acids (miRNAs) are small sequences of genetic materials that are primarily transcribed from the intronic regions of deoxyribonucleic acid (DNAs), and they are pivotal in regulating messenger RNA (mRNA) expression. miRNAs were first discovered to regulate mRNAs of the same cell in which they were transcribed. Recent studies have unveiled their ability to traverse cells, either encapsulated in vesicles or freely bound to proteins, influencing distant recipient cells. Activities of extracellular miRNAs have been observed during acute inflammation in clinically relevant pathologies, such as sepsis, shock, trauma, and ischemia/reperfusion (I/R) injuries. This review comprehensively explores the activity of miRNAs during acute inflammation as well as the mechanisms of their extracellular transport and activity. Evaluating the potential of extracellular miRNAs as diagnostic biomarkers and therapeutic targets in acute inflammation represents a critical aspect of this review. Finally, this review concludes with novel concepts of miRNA activity in the context of alleviating inflammation, delivering potential future directions to advance the field of miRNA therapeutics. [ABSTRACT FROM AUTHOR]

Background: Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. Methods: We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). Results: We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. Conclusions: miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels. [ABSTRACT FROM AUTHOR]

Liver fibrosis is the excessive accumulation of extracellular matrix proteins. Due to the lack of an accurate test for an early diagnosis of liver fibrosis and the invasiveness of the liver biopsy procedure, there is an urgent need for effective non-invasive biomarkers for screening the patients. we aimed to evaluate the diagnostic performance of circulating miRNAs (miR-146b, −194, −214) and their related mechanisms in the pathogenesis of liver fibrosis. The expression levels of miR-146b, −194, and −214 were quantified in whole blood samples from NAFLD patients using real-time PCR. The competing endogenous RNA (ceRNA) network was constructed and a gene set enrichment analysis (GSEA) was performed for HSC activation-related genes. Also, the transcription factor (TF)-miR co-regulatory network and the survival plot for three miRNAs and core genes were illustrated. The qPCR results showed that the relative expression of miR-146b and miR-214 significantly increased in NAFLD patients, while miR-194 showed significant down-regulation. The ceRNA network analysis implicated NEAT1 and XIST as sponge candidates for these miRNAs. The GSEA results identified 15 core genes involved in HSC activation, primarily enriched in NF-κB activation and autophagy pathways. STAT3, TCF3, RELA, and RUNX1 were considered potential transcription factors connected to miRNAs in the TF-miR network. Our study elucidated three candidate circulating miRNAs differentially expressed in NAFLD that could serve as a promising non-invasive diagnostic tool for early detection strategies. Also, NF-κB activation, autophagy, and negative regulation of the apoptotic process are the main potential underlying mechanisms regulated by these miRNAs in liver fibrosis pathogenesis.

Background: Identification of new clinical markers contributes to a better understanding of the pathogenesis of asthma. Considering the crucial role of LIGHT in asthma, it may become a potential target for asthma. The aim of current study was to determine if circulating microRNAs (miRNAs) targeting LIGHT may be used as diagnostic biomarkers to distinguish asthma. Methods: Blood serum from a cohort of 60 subjects, including 20 cases with mild asthma, 20 cases with moderate-to-severe asthma, and 20 healthy controls were included. Serum was analyzed for circulating miRNAs profiles through miRNAs microarray. Real Time PCR was conducted to verify the results of miRNA microarray. Correlations between circulating miRNAs targeting LIGHT and clinical characteristics were investigated. Results: A total of 365 miRNAs were differentially expressed in asthma patients. Among them, miR-107 and miR-140-5p were found to target LIGHT, and varied in asthmatics. Additionally, miR-107 and miR-140-5p expressions were positively correlated with the absolute value of peripheral eosinophils. Finally, miR-140-5p and miR-107 were demonstrated to have good diagnostic efficacy for asthma (AUC= 0.8667 and 0.9400) with good sensitivity (0.8000 and 0.8667, respectively) and specificity (0.8667 and 0.867). Thus, circulating miRNAs expressed differentially between healthy control and asthma patients. Conclusion: Plasma miR-140-5p and miR-107 can be used as diagnostic biomarkers to distinguish patients with asthma from healthy control, and may take part in asthma pathogenesis by negatively regulating LIGHT. Further research was needed to evaluate their roles as potential biomarkers in the diagnosis of asthma. [ABSTRACT FROM AUTHOR]

Purpose: The lack of clinical markers prevents early diagnosis of glioblastoma (GBM). Many studies have found that circulating microRNAs (miRNAs) can be used as early diagnostic markers of malignant tumours. Therefore, the identification of novel circulating miRNA biomolecular markers could be beneficial to clinicians in the early diagnosis of GBM. Methods: We developed a decision tree joint scoring algorithm (DTSA), systematically integrating significance analysis of microarray (SAM), Pearson hierarchical clustering, T test, Decision tree and Entropy weight score algorithm, to screen out circulating miRNA molecular markers with high sensitivity and accuracy for early diagnosis of GBM. Results: DTSA was developed and applied for GBM datasets and three circulating miRNA molecular markers were identified, namely, hsa-miR-2278, hsa-miR-555 and hsa-miR-892b. We have found that hsa-miR-2278 and hsa-miR-892b regulate the GBM pathway through target genes, promoting the development of GBM and affecting the survival of patients. DTSA has better classification effect in all data sets than other classification algorithms, and identified miRNAs are better than existing markers of GBM. Conclusion: These results suggest that DTSA can effectively identify circulating miRNA, thus contributing to the early diagnosis and personalised treatment of GBM. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer represents the most prevalent malignancy among women. Recent advancements in translational research have focused on the identification of novel biomarkers capable of providing valuable insights into patient outcomes. Furthermore, comprehensive investigations aimed at discovering novel miRNAs, unraveling their biological functions, and deciphering their target genes have significantly contributed to our understanding of the roles miRNAs play in tumorigenesis. Consequently, these investigations have facilitated the way for the development of miRNA-based approaches for breast cancer prognosis, diagnosis, and treatment. However, conducting a more extensive array of studies, particularly among diverse ethnic groups, is imperative to expand the scope of research and validate the significance of miRNAs. This study aimed to assess the expression patterns of circulating miRNAs in plasma as a prospective biomarker for breast cancer patients within a population primarily consisting of individuals from Black, Indigenous, and People of Color (BIPOC) communities.Methods: We evaluated 49 patients with breast cancer compared to 44 healthy women.Results and discussion: All miRNAs analyzed in the plasma of patients with breast cancer were downregulated. ROC curve analysis of miR-21 (AUC = 0.798, 95% CI: 0.682–0.914, p

MicroRNAs (miRNAs) play a crucial role in the early diagnosis of autoinflammatory diseases, with Hidradenitis Suppurativa (HS) being a notable example. HS, an autoinflammatory skin disease affecting the pilosebaceous unit, profoundly impacts patients’ quality of life. Its hidden nature, with insidious initial symptoms and patient reluctance to seek medical consultation, often leads to a diagnostic delay of up to 7 years. Recognizing the urgency for early diagnostic tools, recent research identified significant differences in circulating miRNA expression, including miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p, between HS patients and healthy controls. These miRNAs serve as potential biomarkers for earlier disease detection. Traditional molecular biology techniques, like reverse transcription quantitative-polymerase chain reaction (RT-qPCR), are employed for their detection using specific primers and probes. Alternatively, short peptides offer a versatile and effective means for capturing miRNAs, providing specificity, ease of synthesis, stability, and multiplexing potential. In this context, we present a computational simulation pipeline designed for crafting peptide sequences that can capture circulating miRNAs in the blood of patients with autoinflammatory skin diseases, including HS. This innovative approach aims to expedite early diagnosis and enhance therapeutic follow-up, addressing the critical need for timely intervention in HS and similar conditions.

IntroductionIt is well-known that circulating microRNAs (miRNAs) play a relevant role in many kinds of diseases by regulating the expression of genes involved in various pathophysiologic processes, including erectile dysfunction (ED) and cardiovascular diseases (CVD).PurposeThis study aimed to identify the miRNA-21 profile in the blood samples of patients with ED, CVD, and the combination of both pathologies to elucidate the potential function of miRNA-21.MethodsA total of 45 patients with CVD and/or who underwent the erectile function test were included and divided into the following categories: CVD with ED (cases, n = 29) and controls (n = 16) with either ED or CVD. Real-time polymerase chain reaction analysis verified the results. miRNA-21 expression was quantified, and informatics analysis was applied to predict the functions of this differentially expressed miRNA-21.ResultsA total of 64% of cases (63 ± 9 years, 66% with severe ED, 56% with CV ejection fraction) first presented ED as the sentinel clinical manifestation. Serum miRNA-21 levels in the control ED were significant, up to 10-fold higher than in the CVD controls and cases. A significant inverse (p = 0.0368, β = −2.046) correlation was found between erectile function and miRNA-21 levels.ConclusionsOur study provides comprehensive insights into the functional interaction between miRNA-21 and ED in CVD patients. Its relevance lies in the potential of miRNA as a biomarker to be applied in the cardiovascular predictive medicine field.

Abstract Objective A meta-analysis was conducted to assess the impact of miRNAs in circulation on diagnosing benign and malignant pulmonary nodules (BPNs and MPNs). Methods Electronic databases such as Embase, PubMed, Web of Science, and The Cochrane Library were utilized for diagnostic tests of circulating miRNAs to diagnose BPNs and MPNs from the library creation to February 2023. Meta-analysis of the included literature was performed using Stata 16, Meta-Disc 1.4, and Review Manager 5.4 software. This study determined the combined sensitivity, specificity, diagnostic ratio (DOR), positive/negative likelihood ratios (PLR/NLR), as well as value of area under the receiver operating characteristic (ROC) curve. Results This meta-analysis included 14 publications and 17 studies. According to our findings, the pooled sensitivity for miRNA in diagnosing benign and malignant pulmonary nodules was 0.82 [95% CI (0.74, 0.88)], specificity was 0.84 [95% CI (0.79, 0.88)], whereas the DOR was 22.69 [95% CI (13.87, 37.13)], PLR was 5.00 [95% CI (3.87, 6.46)], NLR was 0.22 [95% CI (0.15, 0.32)], and the area under the working characteristic curve (AUC) of the subject was 0.89 [95% CI (0.86, 0.91)]. Conclusion Circulating miRNAs could be used with sensitivity, specificity, DOR, PLR, NLR, and AUC as biomarkers to diagnose pulmonary nodules (PNs). However, more research is needed to determine the optimum miRNA combinations for diagnosing PNs due to the significant heterogeneity on previous studies.

Background: Wilms tumour (WT) is caused by aberrant embryonic kidney development and associated with dysregulated expression of short, non-protein-coding RNAs termed microRNAs (miRNAs). At present, there is no reliable circulating biomarker of WT, and this remains an urgent unmet clinical need. Such biomarkers may assist diagnosis, subtyping/prognostication, and disease-monitoring. Here, we established the list of dysregulated circulating miRNAs in WT from the existing published literature. Methods: Regardless of publication date, PubMed, Scopus, Web-of-Science, and Wiley online library databases were searched for English/French studies on WT circulating miRNAs. The PRISMA-compliant search was registered in PROSPERO. The QUADAS tool measured retained article quality. The meta-analysis assessed the sensitivity and specificity of miRNAs for WT diagnosis. Results: Qualitative analysis included 280 samples (172 WT patients; 108 healthy controls) from five of 450 published articles. The study uncovered 301 dysregulated miRNAs (144 up-regulated, 143 down-regulated, 14 conflicting). The pooled sensitivity, specificity, and AUC of the 49 significantly dysregulated microRNAs from two studies was 0.67 [0.62; 0.73], 0.95 [0.92; 0.96] and 0.77 [0.73; 0.81] respectively, indicating a stronger diagnostic potential for WT. Conclusions: Circulating miRNAs show promise for WT diagnosis and prognosis. More research is needed to confirm these findings and determine associations with tumour stage/subtype. Prospero registration number: CRD42022301597.

Micro ribonucleic acid (miRNA) is single-stranded RNAs that play a key role in gene regulation and development. The origin and precise activities of miRNAs have been uncovered in recent years, with an emphasis on their potential applications in the research field. Thus, miRNAs are promising diagnostic and prognostic biomarkers especially disease specific biomarker. Traditional methods for detection of miRNA lack sensitivity and specificity. Therefore, novel nanotechnology-based methods to detect microRNA have been developed. This literature review provides an overview of cutting edge nano approaches that have been used to identify distinct miRNA biomarkers. To date, no single or panel of miRNA marker has been developed for clinical application. Therefore, further research is needed on the detection of multiple miRNA biomarkers to diagnose various diseases at an early stage using nanotechnology.

BackgroundIdentification of new clinical markers contributes to a better understanding of the pathogenesis of asthma. Considering the crucial role of LIGHT in asthma, it may become a potential target for asthma. The aim of current study was to determine if circulating microRNAs (miRNAs) targeting LIGHT may be used as diagnostic biomarkers to distinguish asthma.MethodsBlood serum from a cohort of 60 subjects, including 20 cases with mild asthma, 20 cases with moderate-to-severe asthma, and 20 healthy controls were included. Serum was analyzed for circulating miRNAs profiles through miRNAs microarray. Real Time PCR was conducted to verify the results of miRNA microarray. Correlations between circulating miRNAs targeting LIGHT and clinical characteristics were investigated.ResultsA total of 365 miRNAs were differentially expressed in asthma patients. Among them, miR-107 and miR-140-5p were found to target LIGHT, and varied in asthmatics. Additionally, miR-107 and miR-140-5p expressions were positively correlated with the absolute value of peripheral eosinophils. Finally, miR-140-5p and miR-107 were demonstrated to have good diagnostic efficacy for asthma (AUC= 0.8667 and 0.9400) with good sensitivity (0.8000 and 0.8667,respectively) and specificity (0.8667 and 0.867). Thus, circulating miRNAs expressed differentially between healthy control and asthma patients.ConclusionPlasma miR-140-5p and miR-107 can be used as diagnostic biomarkers to distinguish patients with asthma from healthy control, and may take part in asthma pathogenesis by negatively regulating LIGHT. Further research was needed to evaluate their roles as potential biomarkers in the diagnosis of asthma.

Simple Summary: Monitoring animals' welfare is a tricky challenge. The responsiveness to stressors is subjective and its magnitude varies among species, breeds, and individuals. Small molecules named miRNAs obtained from body fluid samples are promising biomarkers to classify animal welfare. Under common farming conditions, we identified several miRNAs in the saliva of ewes. Based on the concentration and trend of individual salivary cortisol, one of the molecules historically recognized and used to define the stress level in vertebrates, we divided the animals into two clusters. The expression of two miRNAs involved in regulating genes related to the stress pathway resulted in significant differences between the two phenotypes, and their trends were correlated. These results have produced objective data to improve the knowledge about sheep physiology and the basis to develop new tools for welfare assessment. In the animal production field, the assessment of biomarkers that are useful in identifying individuals with different levels of vulnerability or resiliency to stress stimuli may help to introduce new strategies in animal farms and genetic research for the selection of animals. Farm procedures have an impact on animal welfare by activating the hypothalamic-pituitary-adrenal axis that induces a wide array of physiological responses. This adaptive system guarantees that the animal copes with environmental variations and it induces metabolic and molecular changes that can be quantified. MicroRNAs (miRNAs) play a key role in the regulation of homeostasis and emerging evidence has identified circulating miRNAs as promising biomarkers of stress-related disorders in animals. Based on a clustering analysis of salivary cortisol trends and levels, 20 ewes were classified into two different clusters. The introduction of a ram in the flock was identified as a common farm practice and reference time point to collect saliva samples. Sixteen miRNAs related to the adaptation response were selected. Among them, miR-16b, miR-21, miR-24, miR-26a, miR-27a, miR-99a, and miR-223 were amplified in saliva samples. Cluster 1 was characterized by a lower expression of miR-16b and miR-21 compared with Cluster 2 (p < 0.05). This study identified for the first time several miRNAs expressed in sheep saliva, pointing out significant differences in the expression patterns between the cortisol clusters. In addition, the trend analyses of these miRNAs resulted in clusters (p = 0.017), suggesting the possible cooperation of miR-16b and -21 in the integrated stress responses, as already demonstrated in other species as well. Other research to define the role of these miRNAs is needed, but the evaluation of the salivary miRNAs could support the selection of ewes for different profiles of response to sources of stressors common in the farm scenario. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of legal medicine. It is not easy to determine the cause in a SCD case and the available methods used for diagnosis cannot always give an exhaustive answer. In addition, the molecular analysis of genes does not lead to a clear conclusion, but it could be interesting to focus attention on the expression level of miRNAs, a class of non-coding RNA of about 22 nucleotides. The role of miRNAs is to regulate the gene expression through complementary binding to 3′-untraslated regions of miRNAs, leading to the inhibition of translation or to mRNA degradation. In recent years, several studies were performed with the aim of exploring the use of these molecules as biomarkers for SCD cases, and to also distinguish the causes that lead to cardiac death. In this review, we summarize experiments, evidence, and results of different studies on the implication of miRNAs in SCD cases. We discuss the different biological starting materials with their respective advantages and disadvantages, studying miRNA expression on tissue (fresh-frozen tissue and FFPE tissue), circulating cell-free miRNAs in blood of patients affected by cardiac disease at high risk of SCD, and exosomal miRNAs analyzed from serum of people who died from SCD. [ABSTRACT FROM AUTHOR]

Objective: A meta-analysis was conducted to assess the impact of miRNAs in circulation on diagnosing benign and malignant pulmonary nodules (BPNs and MPNs). Methods: Electronic databases such as Embase, PubMed, Web of Science, and The Cochrane Library were utilized for diagnostic tests of circulating miRNAs to diagnose BPNs and MPNs from the library creation to February 2023. Meta-analysis of the included literature was performed using Stata 16, Meta-Disc 1.4, and Review Manager 5.4 software. This study determined the combined sensitivity, specificity, diagnostic ratio (DOR), positive/negative likelihood ratios (PLR/NLR), as well as value of area under the receiver operating characteristic (ROC) curve. Results: This meta-analysis included 14 publications and 17 studies. According to our findings, the pooled sensitivity for miRNA in diagnosing benign and malignant pulmonary nodules was 0.82 [95% CI (0.74, 0.88)], specificity was 0.84 [95% CI (0.79, 0.88)], whereas the DOR was 22.69 [95% CI (13.87, 37.13)], PLR was 5.00 [95% CI (3.87, 6.46)], NLR was 0.22 [95% CI (0.15, 0.32)], and the area under the working characteristic curve (AUC) of the subject was 0.89 [95% CI (0.86, 0.91)]. Conclusion: Circulating miRNAs could be used with sensitivity, specificity, DOR, PLR, NLR, and AUC as biomarkers to diagnose pulmonary nodules (PNs). However, more research is needed to determine the optimum miRNA combinations for diagnosing PNs due to the significant heterogeneity on previous studies. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic biomarkers. Since microRNAs (miRNAs) contribute to oncogenesis and metastasis formation in PDAC, they are considered potential candidates for fulfilling this task. In this work, the levels of two miRNA subsets (involved in chemoresistance or with oncogenic/tumor suppressing functions) were investigated in a panel of PDAC cell lines and liquid biopsies of a small cohort of patients. We used RT-qPCR and droplet digital PCR (ddPCR) to measure the amounts of cellular- and vesicle-associated, and circulating miRNAs. We found that both PDAC cell lines, also after gemcitabine treatment, and patients showed low amounts of cellular-and vesicle-associated miR-155-5p, compared to controls. Interestingly, we did not find any differences when we analyzed circulating miR-155-5p. Furthermore, vesicle-related miR-27a-3p increased in cancer patients compared to the controls, while circulating let-7a-5p, miR-221-3p, miR-23b-3p and miR-193a-3p presented as dysregulated in patients compared to healthy individuals. Our results highlight the potential clinical significance of these analyzed miRNAs as non-invasive diagnostic molecular tools to characterize PDAC.

Metabolic dysfunction-associated steatotic liver disease (MASLD), with a prevalence of 30% of adults globally, is considered a multifactorial disease. There is a lack of effective non-invasive methods for accurate diagnosis and monitoring. Therefore, this study aimed to explore associations between changes in circulating miRNA levels, inflammatory markers, and depressive symptoms with hepatic variables in MASLD subjects and their combined potential to predict the disease after following a dietary intervention. Biochemical markers, body composition, circulating miRNAs and hepatic and psychological status of 55 subjects with MASLD with obesity and overweight from the FLiO study were evaluated by undergoing a 6-, 12- and 24-month nutritional intervention. The highest accuracy values of combined panels to predict the disease were identified after 24 months. A combination panel that included changes in liver stiffness, high-density lipoprotein cholesterol (HDL-c), body mass index (BMI), depressive symptoms, and triglycerides (TG) yielded an AUC of 0.90. Another panel that included changes in hepatic fat content, total cholesterol (TC), miR15b-3p, TG, and depressive symptoms revealed an AUC of 0.89. These findings identify non-invasive biomarker panels including circulating miRNAs, inflammatory markers, depressive symptoms and other metabolic variables for predicting MASLD presence and emphasize the importance of precision nutrition in MASLD management and the sustained adherence to healthy lifestyle patterns.

Micro-ribonucleic acids (miRNAs) are small sequences of genetic materials that are primarily transcribed from the intronic regions of deoxyribonucleic acid (DNAs), and they are pivotal in regulating messenger RNA (mRNA) expression. miRNAs were first discovered to regulate mRNAs of the same cell in which they were transcribed. Recent studies have unveiled their ability to traverse cells, either encapsulated in vesicles or freely bound to proteins, influencing distant recipient cells. Activities of extracellular miRNAs have been observed during acute inflammation in clinically relevant pathologies, such as sepsis, shock, trauma, and ischemia/reperfusion (I/R) injuries. This review comprehensively explores the activity of miRNAs during acute inflammation as well as the mechanisms of their extracellular transport and activity. Evaluating the potential of extracellular miRNAs as diagnostic biomarkers and therapeutic targets in acute inflammation represents a critical aspect of this review. Finally, this review concludes with novel concepts of miRNA activity in the context of alleviating inflammation, delivering potential future directions to advance the field of miRNA therapeutics.

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Micro ribonucleic acid (miRNA) is single-stranded RNAs that play a key role in gene regulation and development. The origin and precise activities of miRNAs have been uncovered in recent years, with an emphasis on their potential applications in the research field. Thus, miRNAs are promising diagnostic and prognostic biomarkers especially disease specific biomarker. Traditional methods for detection of miRNA lack sensitivity and specificity. Therefore, novel nanotechnology-based methods to detect microRNA have been developed. This literature review provides an overview of cutting edge nano approaches that have been used to identify distinct miRNA biomarkers. To date, no single or panel of miRNA marker has been developed for clinical application. Therefore, further research is needed on the detection of multiple miRNA biomarkers to diagnose various diseases at an early stage using nanotechnology. [ABSTRACT FROM AUTHOR]

Early detection of cancers and their precise subtyping are essential to patient stratification and effective cancer management. Data-driven identification of expression biomarkers coupled with microfluidics-based detection shows promise to revolutionize cancer diagnosis and prognosis. MicroRNAs play key roles in cancers and afford detection in tissue and liquid biopsies. In this review, we focus on the microfluidics-based detection of miRNA biomarkers in AI-based models for early-stage cancer subtyping and prognosis. We describe various subclasses of miRNA biomarkers that could be useful in machine-based predictive modeling of cancer staging and progression. Strategies for optimizing the feature space of miRNA biomarkers are necessary to obtain a robust signature panel. This is followed by a discussion of the issues in model construction and validation towards producing Software-as-Medical-Devices (SaMDs). Microfluidic devices could facilitate the multiplexed detection of miRNA biomarker panels, and an overview of the different strategies for designing such microfluidic systems is presented here, with an outline of the detection principles used and the corresponding performance measures. Microfluidics-based profiling of miRNAs coupled with SaMD represent high-performance point-of-care solutions that would aid clinical decision-making and pave the way for accessible precision personalized medicine. [ABSTRACT FROM AUTHOR]

Abstract Objective In quantitative reverse transcription‐polymerase chain reaction (RT‐qPCR) studies, the selection and validation of reference genes are crucial for the accurate analysis of MicroRNAs (miRNAs) expression. In this work, the optimal reference genes for RT‐qPCR normalisation in plasma samples of rat middle cerebral artery occlusion (MCAO) models were identified. Methods Six rat MCAO models were established. Blood samples were collected before modelling and approximately 16–24 h after modelling. Two commonly used reference genes (U6 and 5S) and three miRNAs (miR‐24, miR‐122 and miR‐9a) were selected as candidate reference genes, and the expression of these genes was detected with RT‐qPCR. The acquired data were analysed using geNorm, Normfinder, BestKeeper, RefFinder and comparative delta threshold cycle statistical models. Results The analysed results consistently showed that miR‐24 was the most stably expressed reference gene. The ‘optimal combination’ calculated by geNorm was miR‐24, U6 and5S. The expression level of the target gene miR124 was similar when the most stable reference gene miR‐24 or the ‘optimal combination’ was used as a reference gene. However, compared with miR24 or the ‘optimal combination’, the less stable reference genes influenced the fold change and the data accuracy with a large standard deviation. Conclusion These results confirmed the importance of selecting suitable reference genes for normalisation to obtain reliable results in RT‐qPCR studies and demonstrated that the identified reference gene miR‐24 or the ‘optimal combination’ could be used as an internal control for gene expression analysis in the rat MCAO model.

Copyright of Pamukkale Medical Journal is the property of Pamukkale Journal of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pancreatic cancer (PC) is considered to be the seventh most common cause of cancer-related deaths. The number of deaths caused by PC is estimated to increase in the future. An early diagnosis of PC is crucial for improving treatment outcomes. The most common histopathological subtype of PC is pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miRNAs)—which are endogenous non-coding RNAs involved in the posttranscriptional regulation of multiple gene expression—constitute useful diagnostic and prognostic biomarkers in various neoplasms, including PDAC. Circulating miRNAs detected in a patient's serum or plasma are drawing more and more attention. Hence, this review aims at evaluating the clinical value of circulating miRNA in the screening, diagnosis, prognosis and monitoring of pancreatic ductal adenocarcinoma therapy. [ABSTRACT FROM AUTHOR]

Background: Walking is the preferred therapy for peripheral arterial disease in early stage. An effect of walking exercise is the increase of blood flow and fluid shear stress, leading, triggered by arteriogenesis, to the formation of collateral blood vessels. Circulating micro-RNA may act as an important information transmitter in this process. We investigated the acute effects of a single bout of 1) aerobic walking with moderate intensity; and 2) anaerobic walking with vigorous intensity on miRNA parameters related to vascular collateral formation. Methods: Ten (10) patients with peripheral arterial disease with claudication (age 72 ± 7 years) participated in this two-armed, randomized-balanced cross-over study. The intervention arms were single bouts of supervised walking training at (1) vigorous intensity on a treadmill up to volitional exhaustion and (2) moderate intensity with individual selected speed for a duration of 20 min. One week of washout was maintained between the arms. During each intervention, heart rate was continuously monitored. Acute effects on circulating miRNAs and lactate concentration were determined using pre- and post-intervention measurement comparisons. Results: Vigorous-intensity walking resulted in a higher heart rate (125 ± 21 bpm) than the moderate-intensity intervention (88 ± 9 bpm) (p < 0.05). Lactate concentration was increased after vigorous-intensity walking (p = 0.005; 3.3 ± 1.2 mmol/l), but not after moderate exercising (p > 0.05; 1.7 ± 0.6 mmol/l). The circulating levels of miR-142-5p and miR-424-5p were up-regulated after moderate-intensity (p < 0.05), but not after vigorous-intensity training (p > 0.05). Conclusion: Moderate-intensity walking seems to be more feasible than vigorous exercises to induce changes of blood flow and endurance training-related miRNAs in patients with peripheral arterial disease. Our data thus indicates that effect mechanisms might follow an optimal rather than a maximal dose response relation. Steady state walking without the necessity to reach exhaustion seems to be better suited as stimulus. [ABSTRACT FROM AUTHOR]

Abstract Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.

Simple Summary: Circulating miRNAs are not only present in cells but also in the extracellular environment, especially in different biofluids including blood, and can act in a paracrine manner by facilitating a diversity of signaling mechanisms between cells. In qPCR gene expression profiling analysis, the endogenous control must be a stable gene to allow an accurate cross-sample gene expression comparison. The appropriate selection of an endogenous control is a crucial step. This research aims to select, in the miRNome, appropriate circulating miRNAs that can serve as an endogenous control. The study model are working dogs used in the search and rescue of missing persons after natural disasters. Cell-free miRNAs, called circulating miRNAs (cmiRNAs), can act in a paracrine manner by facilitating a diversity of signaling mechanisms between cells. Real-time qPCR is the most accepted method for quantifying miRNA expression levels. The use of stable miRNA endogenous control (EC) for qPCR data normalization allows an accurate cross-sample gene expression comparison. The appropriate selection of EC is a crucial step because qPCR data can change drastically when normalization is performed using an unstable versus a stable EC. To find EC cmiRNA with stable expression in search and rescue (SAR) working dogs, we explored the serum miRNome by Next-Generation Sequencing (NGS) at T0 (resting state) and T1 immediately after SAR performance (state of physiologically recovered stress). The cmiRNAs selected in the NGS circulating miRNome as probable ECs were validated by qPCR, and miRNA stability was evaluated using the Delta Ct, BestKeeper, NormFinder, and GeNorm algorithms. Finally, RefFinder was used to rank the stability orders at both T0 and T1 by establishing miR-320 and miR-191 as the best-circulating ECs. We are confident that this study not only provides a helpful result in itself but also an experimental design for selecting the best endogenous controls to normalize gene expression for genes beyond circulating miRNAs. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow (BM) microenvironment. Despite the progress made in treatment, some MM patients still die within the first year of diagnosis. Numerous studies investigating microRNA (miRNA) expression patterns suggest they may be good prognostic markers. The primary aim of this study was to analyze the expression of selected miRNAs in the serum of MM patients who were later treated with bortezomib-based regimens, and to determine their potential to predict early mortality. The study was conducted in 70 prospectively recruited patients with newly diagnosed MM admitted to the Department of Hematology of the Copernicus Memorial Hospital, Lodz (Poland) between 2017 and 2021. Among them, 17 patients experienced death within 12 months of diagnosis. The expression of 31 selected miRNAs was determined using a miRCURY LNA miRNA Custom PCR Panel. The obtained clinical data included patient characteristics on diagnosis, treatment regimen, response to treatment, and follow-up. Differential expression analysis found two miRNAs to be significantly downregulated in the early mortality group: hsa-miR-328-3p (fold change—FC: 0.72, p = 0.0342) and hsa-miR-409-3p (FC: 0.49, p = 0.0357). Univariate and multivariate logistic regression analyses were performed to assess the early mortality rate. The final model consisted of hsa-miR-409-3p, hsa-miR-328-3p, age, and R-ISS 3. It yielded an area under the curve (AUC) of 0.863 (95%CI: 0.761–0.965) with 88.2% sensitivity and 77.5% specificity. Further external validation of our model is needed to confirm its clinical value. [ABSTRACT FROM AUTHOR]

miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised that miRNA dysregulation reflects the state and function of cells and tissues, contributing to their dysfunction. The identification of hundreds of extracellular miRNAs in biological fluids has underscored their potential in the field of biomarker research. In addition, the therapeutic potential of miRNAs is receiving increasing attention in numerous conditions. On the other hand, many operative problems including stability, delivery systems, and bioavailability, still need to be solved. In this dynamic field, biopharmaceutical companies are increasingly engaged, and ongoing clinical trials point to anti-miR and miR-mimic molecules as an innovative class of molecules for upcoming therapeutic applications. This article aims to provide a comprehensive overview of current knowledge on several pending issues and new opportunities offered by miRNAs in the treatment of diseases and as early diagnostic tools in next-generation medicine. [ABSTRACT FROM AUTHOR]

Circulating hsa-miRNA-126 (CmiR-126) has been reported to involve in the pathogenesis of many infectious diseases including dengue virus infection. However, no prior study has been conducted to describe more details in dengue-infected pediatric patients. This study aimed to describe CmiR-126-3p in dengue-infected pediatric patients during the febrile and convalescent phases. Additionally, the correlations between CmiR-126-3p and other relevant clinical laboratory factors were investigated. Sixty paired-serum specimens collected during febrile and convalescent phases were retrieved from patients with dengue fever (DF) (n = 30) and dengue hemorrhagic fever (DHF) (n = 30). Thirty paired-serum specimens collected from non-dengue acute febrile illness patients (AFI) were included as the control group. CmiR-126-3p was determined using reverse transcription quantitative real-time polymerase-chain reaction (RT-qPCR). Relative miRNA expression was calculated as 2−ΔCt using CmiR-16-5p for data normalization. CmiR-126-3p expression during febrile and convalescent phases in dengue-infected patients was significantly lower than AFI (p < 0.05). However, miRNA levels were not different (p > 0.05) compared between DF and DHF and between primary and secondary infection. CmiR-126-3p levels in DF in the convalescent were significantly higher than in the febrile phase (p = 0.025). No association between CmiR-126-3p and hematocrit, WBC level, platelet count, WBC differential count or dengue viral load was observed (p > 0.05). The data suggest that hsa-miR-126-3p involved in pathogenesis of dengue infection and may be a promising early and late biomarker for DENV infection. However, hsa-miR-126-3p alone cannot be used as a predictor for dengue severity. [ABSTRACT FROM AUTHOR]

Maternal obesity (MO) is expanding worldwide, contributing to the onset of Gestational Diabetes Mellitus (GDM). MO and GDM are associated with adverse maternal and foetal outcomes, with short- and long-term complications. Growing evidence suggests that MO and GDM are characterized by epigenetic alterations contributing to the pathogenesis of metabolic diseases. In this pilot study, plasma microRNAs (miRNAs) of obese pregnant women with/without GDM were profiled at delivery. Nineteen women with spontaneous singleton pregnancies delivering by elective Caesarean section were enrolled: seven normal-weight (NW), six obese without comorbidities (OB/GDM(−)), and six obese with GDM (OB/GDM(+)). miRNA profiling with miRCURY LNA PCR Panel allowed the analysis of the 179 most expressed circulating miRNAs in humans. Data acquisition and statistics (GeneGlobe and SPSS software) and Pathway Enrichment Analysis (PEA) were performed. Data analysis highlighted patterns of significantly differentially expressed miRNAs between groups: OB/GDM(−) vs. NW: n = 4 miRNAs, OB/GDM(+) vs. NW: n = 1, and OB/GDM(+) vs. OB/GDM(−): n = 14. For each comparison, PEA revealed pathways associated with oxidative stress and inflammation, as well as with nutrients and hormones metabolism. Indeed, miRNAs analysis may help to shed light on the complex epigenetic network regulating metabolic pathways in both the mother and the foeto-placental unit. Future investigations are needed to deepen the pregnancy epigenetic landscape in MO and GDM. [ABSTRACT FROM AUTHOR]

The technological advancement in diagnostic techniques has immensely improved the capability of predicting disease progression. Yet, there is a great interest in developing newer biomarkers that can enhance disease risk prediction thereby minimising the associated morbidity and mortality. Circulating miRNAs, a non-coding RNA molecule, are critical regulators in the pathophysiology of various complex multifactorial diseases. In recent years, circulating miRNAs have been enormously studied and are considered as an emerging biomarker due to their easy accessibility, stability, and detection by sequence-specific amplification methods. However, there is a distinct lack of consensus regarding the preanalytical factors such as preferred sample selection, methodological aspects, etc that may independently or together influence the detection of circulating miRNAs resulting in erroneous expression profiles. Therefore, the present review makes an attempt to highlight the various pre-analytical and analytical factors that can potentially influence the circulating miRNA levels. Literature on circulating miRNA's stability, processing and quantitation in different biofluids along with the effect of various controllable and uncontrollable factors influencing circulating miRNA expression have been summarised in the current review. [ABSTRACT FROM AUTHOR]

Background: Hepatic resection, radiofrequency ablation (RF), and liver transplantation (LT) represent the only available curative treatments for early stage hepatocellular carcinoma (HCC). Various studies showed that the 5-year overall survival (OS) rate reaches ∼70% after resection and ∼60% after RF. Objective: To improve the success rate of curative therapies and consequently the OS, an improvement in patients’ selection and management should be pursued. In this regard, microRNAs (miRNAs) can be helpful prognostic biomarkers. Materials and Methods: In this retrospective study, a miRNA array profiling was performed on 34 HCC blood samples which is collected before therapy (T0), 1 month (T1), and 6 months (T2) after curative treatments (resection and RF) to identify noninvasive biomarker candidates for therapy response and OS. MiRNAs were validated in 80 blood HCC samples using quantitative real-time PCR (qRT-PCR). Patients were divided into complete responder (CR) and partial responder and progressive disease (PRPD). Results: Among the selected miRNAs, miR-3201 is significantly associated with treatment response in the validation phase, showing a 23% reduction (P = .026) in CR compared to PRPD. MiR-3201 was able to distinguish CR from PRPD (area under the curve [AUC] = 0.69, 71% sensitivity, 70% specificity, P = .0036). Furthermore, lower levels of miR-3201 were associated with longer OS (hazard ratio [HR] = 2.61, P = .0006). Conclusions: Blood miR-3201 could be used as a prognostic biomarker for curative therapy response and OS in HCC. [ABSTRACT FROM AUTHOR]

Detecting breast cancer (BC) at the initial stages of progression has always been regarded as a lifesaving intervention. With modern technology, extensive studies have unraveled the complexity of BC, but the current standard practice of early breast cancer screening and clinical management of cancer progression is still heavily dependent on tissue biopsies, which are invasive and limited in capturing definitive cancer signatures for more comprehensive applications to improve outcomes in BC care and treatments. In recent years, reviews and studies have shown that liquid biopsies in the form of blood, containing free circulating and exosomal microRNAs (miRNAs), have become increasingly evident as a potential minimally invasive alternative to tissue biopsy or as a complement to biomarkers in assessing and classifying BC. As such, in this review, the potential of miRNAs as the key BC signatures in liquid biopsy are addressed, including the role of artificial intelligence (AI) and machine learning platforms (ML), in capitalizing on the big data of miRNA for a more comprehensive assessment of the cancer, leading to practical clinical utility in BC management. [ABSTRACT FROM AUTHOR]

Early detection followed by efficient treatment still remain a considerable challenge for osteosarcoma (OS), indicating the importance of emerging innovative diagnostic methods. Circulating miRNAs offer a promising and non-invasive approach to assess the OS molecular landscapes. This study utilized RNAseq data from OS plasma miRNA expression profiles (PRJEB30542) and PCR Array data (GSE65071) from GEO and ENA databases. In total, 43 miRNAs demonstrated significant differential expression in OS samples of training dataset. A diagnostic model, including hsa-miR-30a-5p, hsa-miR-556–3p, hsa-miR-200a-3p, and hsa-miR-582–5p was identified through multivariate logistic regression analysis and demonstrated significant efficacy in differentiating OS patients from healthy controls in the validation group (AUC: 0.917, sensitivity: 1, specificity: 0.85). The result of target gene prediction and functional enrichment analyses revealed significant associations with terms such as epithelial morphogenesis, P53 and Wnt signaling pathways, and neoplasm metastasis. Further bioinformatics-based evaluations showed that the down-regulation of these miRNAs significantly correlates with poor prognosis and lower survival rate in OS patients and propose their tumor suppressor function in pathogenesis of OS. Furthermore, the study developed a miRNA-mRNA subnetwork that connects these miRNAs to the P53 and Wnt signaling pathways, which are critical pathways with oncogenic effects on OS progression. This comprehensive approach not only presents a promising diagnostic model but also proposes potential molecular markers for OS early diagnosis, making prognosis, and targeted therapy. The identified miRNA-mRNA functional axis holds promise as a valuable resource for further research in understanding OS pathogenesis and establishing therapeutic modalities. [Display omitted] [ABSTRACT FROM AUTHOR]

Angiogenesis is mainly regulated by the delivery of VEGF-dependent signaling to cells. However, the angiogenesis mechanism regulated by VEGF-induced miRNA is still not understood. After VEGF treatment in HUVECs, we screened the changed miRNAs through small-RNA sequencing and found VEGF-induced miR-4701-3p. Furthermore, the GFP reporter gene was used to reveal that TOB2 expression was regulated by miR-4701-3p, and it was found that TOB2 and miR-4701-3p modulation could cause angiogenesis in an in-vitro angiogenic assay. Through the luciferase assay, it was confirmed that the activation of the angiogenic transcription factor MEF2 was regulated by the suppression and overexpression of TOB2 and miR-4701-3p. As a result, MEF2 downstream gene mRNAs that induce angiogenic function were regulated. We used the NCBI GEO datasets to reveal that the expression of TOB2 and MEF2 was significantly changed in cardiovascular disease. Finally, it was confirmed that the expression of circulating miR-4701-3p in the blood of myocardial infarction patients was remarkably increased. In patients with myocardial infarction, circulating miR-4701-3p was increased regardless of age, BMI, and sex, and showed high AUC levels in specificity and sensitivity analysis (AUROC) (AUC = 0.8451, 95 % CI 0.78–0.90). Our data showed TOB2-mediated modulation of MEF2 and its angiogenesis by VEGF-induced miR-4701-3p in vascular endothelial cells. In addition, through bioinformatics analysis using GEO data, changes in TOB2 and MEF2 were revealed in cardiovascular disease. We suggest that circulating miR-4701-3p has high potential as a biomarker for myocardial infarction. [Display omitted] • In this study, we aimed to elucidate a novel mechanism by VEGF-induced miRNA in vascular endothelial cells. • Circulating miRNA 4701-3p binds to TOB2 3' UTR with high efficiency through the target prediction tool. • Circulating miRNA 4701-3p regulate the angiogenic transcription factor MEF2 activity in vascular endothelial cells. • The expression of circulating miR-4701-3p for MI showed a high AUC level (AUC=0.8451, 95% CI 0.78-0.90). [ABSTRACT FROM AUTHOR]

Neuroendocrine Carcinomas (NECs) prognosis is poor.No standard second-line therapy is currently recognized after failure of platinum-based first-line treatment. FOLFIRI and CAPTEM regimens have shown promising activity in preliminary studies. We aimed to evaluate these regimens in metastatic NEC patients. This is an open-label, multicenter, randomized non-comparative phase II trial to evaluate the activity and safety of FOLFIRI or CAPTEM in metastatic NEC patients. Primary endpoints were the 12 weeks-Disease Control Rate (12w-DCR) by investigator assessment per RECIST v1.1 and safety per CTCAE v5.0. Additional endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients' serum samples were subject to NGS miRNome profiling in comparison with healthy donors to reveal differentially expressed miRNAs as candidate circulating biomarkers. The study was halted for futility at interim analysis, as the minimum 12w-DCR threshold of 10 out of 25 patients required for the first step was not reached. From 06/03/2017 to 18/01/2021, 53 out of 112 patients were enrolled. Median follow-up was 22.6 months (range: 1.4–60.4). The 12w-DCR was 39.1 % in the FOLFIRI arm and 28.0 % in the CAPTEM arm. In the FOLFIRI subgroup the 12-months OS rate was 28.4 % (95 % CI: 12.7–46.5) while in the CAPTEM subgroup it was 32.4 % (95 % CI: 14.9–51.3). The most common G3-G4 side effects were neutropenia (n = 5, 18.5 %) and anemia (n = 2, 7.4 %) for FOLFIRI and G3-G4 thrombocytopenia (n = 2, 8.0 %), G4 nausea/vomiting (n = 1, 4.0 %) for CAPTEM. Three microRNAs emerged as NEC independent predictors. High expression values were found to be significantly associated with decreased PFS and OS. The safety profile of FOLFIRI and CAPTEM was manageable. FOLFIRI and CAPTEM chemotherapy showed comparable activity in the second-line setting after progression on etoposide/platinum. NCT03387592 • No second-line treatment recognized for NEC patients after platinum-based therapy. • This phase II trial investigates activity and safety of second-line treatments in NEC. • FOLFIRI and CAPTEM in second-line setting improve the quality of life of NEC patients. • FOLFIRI or CAPTEM might be used interchangeably according ly to , comorbidities and toxicity profile. • miR-1246, miR-1290 and miR-320c are NEC independent prognostic predictors. [ABSTRACT FROM AUTHOR]

Farm procedures have an impact on animal welfare by activating the hypothalamic-pituitary-adrenal axis that induces a wide array of physiological responses. This adaptive system guarantees that the animal copes with environmental variations and it induces metabolic and molecular changes that can be quantified. MicroRNAs (miRNAs) play a key role in the regulation of homeostasis and emerging evidence has identified circulating miRNAs as promising biomarkers of stress-related disorders in animals. Based on a clustering analysis of salivary cortisol trends and levels, 20 ewes were classified into two different clusters. The introduction of a ram in the flock was identified as a common farm practice and reference time point to collect saliva samples. Sixteen miRNAs related to the adaptation response were selected. Among them, miR-16b, miR-21, miR-24, miR-26a, miR-27a, miR-99a, and miR-223 were amplified in saliva samples. Cluster 1 was characterized by a lower expression of miR-16b and miR-21 compared with Cluster 2 (p < 0.05). This study identified for the first time several miRNAs expressed in sheep saliva, pointing out significant differences in the expression patterns between the cortisol clusters. In addition, the trend analyses of these miRNAs resulted in clusters (p = 0.017), suggesting the possible cooperation of miR-16b and -21 in the integrated stress responses, as already demonstrated in other species as well. Other research to define the role of these miRNAs is needed, but the evaluation of the salivary miRNAs could support the selection of ewes for different profiles of response to sources of stressors common in the farm scenario.

Precise classification of central nervous system (CNS) malignancies is vital for the treatment and prognostication. Identification of noninvasive markers can be of importance to guide treatment decisions and in monitoring treatment response. CNS tumors are classified based on morphology with an essential complement of molecular changes, including mutations, amplifications, and methylation. Neuroimaging is the mainstay for initial diagnosis and monitoring tumor response with obvious limitations of imprecise tumor typing and no information on diagnostic, predictive and prognostic markers. Liquid biopsy has evolved as a diagnostic tool in body fluids and is being investigated as a surrogate for tissue biopsy in managing primary and metastatic brain tumors. Liquid biopsy refers to analyzing biological fluids such as peripheral blood, urine, pleural effusion, ascites, and cerebrospinal fluid (CSF); however, peripheral blood remains the primary source of fluid biopsy. The analytes include cell-free DNA (cfDNA) circulating tumor cells (CTCs), circulating micro RNAs (miRNAs), circulating proteins and extracellular vesicles (EVs). Analysis of these components is actively used for early cancer detection, auxiliary staging, prognosis assessment, detection of minimal residual disease (MRD), and monitoring drug resistance in various solid tumors. In recent years, liquid biopsy has been studied in CNS tumors, and analysis of CTCs and cfDNA have become relevant research topics. In the current review, we have explained the clinical potential of liquid biopsy in CNS tumors to assist in diagnosing and predicting prognosis and response to treatment.

Background & Aims: Liver fibrosis arises from long-term chronic liver injury, accompanied by an accelerated wound healing response with interstitial accumulation of extracellular matrix (ECM). Activated hepatic stellate cells (HSC) are the main source for ECM production. MicroRNA29a (miR-29a) is a crucial antifibrotic miRNA that is repressed during fibrosis, resulting in up-regulation of collagen synthesis. Methods: Intracellular and extracellular miRNA levels of primary and immortalized myofibroblastic HSC in response to profibrogenic stimulation by transforming growth factor β (TGFβ) or platelet-derived growth factor-BB (PDGF-BB) or upon inhibition of vesicular transport and autophagy processes were determined by quantitative polymerase chain reaction. Autophagy flux was studied by electron microscopy, flow cytometry, immunoblotting, and immunocytochemistry. Hepatic and serum miR-29a levels were quantified by using both liver tissue and serum samples from a cohort of chronic hepatitis C virus patients and a murine CCl4 induced liver fibrosis model. Results: In our study, we show that TGFβ and PDGF-BB resulted in decrease of intracellular miR-29a and a pronounced increase of vesicular miR-29a release into the supernatant. Strikingly, miR-29a vesicular release was accompanied by enhanced autophagic activity and up-regulation of the autophagy marker protein LC3. Moreover, autophagy inhibition strongly prevented miR-29a secretion and repressed its targets’ expression such as Col1A1. Consistently, hepatic miR-29a loss and increased LC3 expression in myofibroblastic HSC were associated with increased serum miR-29a levels in CCl4-treated murine liver fibrosis and specimens of hepatitis C virus patients with chronic liver disease. Conclusions: We provide evidence that activation-associated autophagy in HSC induces release of miR-29a, whereas inhibition of autophagy represses fibrogenic gene expression in part through attenuated miR-29a secretion.