Serum microRNAs Research Articles

Exposure to ambient air pollutants, serum miRNA networks, lipid metabolism, and non-alcoholic fatty liver disease in young adults

Background and AimAmbient air pollution (AAP) exposure has been associated with altered blood lipids and liver fat in young adults. MicroRNAs regulate gene expression and may mediate these relationships. This work investigated associations between AAP exposure, serum microRNA networks, lipid profiles, and non-alcoholic fatty liver disease (NAFLD) risk in young adults. MethodsParticipants were 170 young adults (17–22 years) from the Meta-AIR cohort of the Children’s Health Study (CHS). Residential AAP exposure (PM2.5, PM10, NO2, 8-hour maximum O3, redox-weighted oxidative capacity [Oxwt]) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Fasting serum lipids were assayed. Liver fat was imaged by MRI and NAFLD was defined by ≥ 5.5% hepatic fat fraction. Serum microRNAs were measured via NanoString and microRNA networks were constructed by weighted gene correlation network analysis. The first principal component of each network represented its expression profile. Multivariable mixed effects regression models adjusted for sociodemographic, behavioral, and clinical covariates; baseline CHS town code was a random effect. Effects estimates are scaled to one standard deviation of exposure. Mediation analysis explored microRNA profiles as potential mediators of exposure-outcome associations. DIANA-mirPATH identified overrepresented gene pathways targeted by miRNA networks. ResultsPrior-month Oxwt was associated with NAFLD (OR=3.45; p = 0.003) and inversely associated with microRNA Network A (β = −0.016; p = 0.026). Prior-year NO2 was associated with non-HDL-cholesterol (β = 7.13; p = 0.01) and inversely associated with miRNA Network A (β = −0.019; p = 0.022). Network A expression was inversely associated with NAFLD (OR=0.35; p = 0.010) and non-HDL-C (β = −6.94 mg/dL; p = 0.035). Network A members miR-199a/b-3p and miR-130a, which both target fatty acid synthase, mediated 21% of the association between prior-month Oxwt exposure with NAFLD (p = 0.048) and 23.3% of the association between prior-year NO2 exposure and non-HDL-cholesterol (p = 0.026), respectively. ConclusionsExposure to AAP may contribute to adverse lipid profiles and NAFLD risk among young adults via altered expression of microRNA profiles.

Diagnostic Performance of Serum MicroRNAs for ST-Segment Elevation Myocardial Infarction in the Emergency Department.

Prompt diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for initiating timely treatment. MicroRNAs have recently emerged as biomarkers in cardiovascular diseases. This study aimed to evaluate the discriminatory capacity of serum microRNAs in identifying an ischemic origin in patients presenting with chest discomfort to the Emergency Department. The study included 98 participants (78 with STEMI and 20 with nonischemic chest discomfort). Significant differences in the expression levels of miR-133b, miR-126, and miR-155 (but not miR-1, miR-208, and miR-208b) were observed between groups. miR-133b and miR-155 exhibited 97% and 93% sensitivity in identifying STEMI patients, respectively. miR-126 demonstrated a specificity of 90% in identifying STEMI patients. No significant associations were found between microRNAs and occurrence of major adverse cardiovascular events (MACE). However, patients with MACE had higher levels of interleukin (IL)-15, IL-21, IFN-γ-induced protein-10, and N-terminal pro B-type natriuretic peptide compared to non-MACE patients. Overall, there were significant associations among the expression levels of microRNAs. However, microRNAs did not demonstrate associations with either inflammatory markers or cardiovascular risk scores. This study highlights the potential of microRNAs, particularly miR-133b and miR-126, as diagnostic biomarkers for distinguishing patients with STEMI from those presenting with nonischemic chest discomfort to the Emergency Department.

Clinical Value of Circulating microRNAs in Diagnosis and Prognosis of Pancreatic Cancer: A Systematic Review.

Pancreatic cancer (PC) is one of the most common cancers and has a high mortality rate due to high invasiveness and rapid progression. Microribonucleic acid (microRNA) plays an essential role in diagnosing PC in the early stages, which improves the five-year survival rate. This systematic review aims to highlight the different subtypes of serum and plasma microRNAs and panel-based assays of microRNAs and how they play a crucial role in the diagnosis and prognosis of PC as a high-sensitive and specific novel biomarker. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines, an in-depth search was performed by using regular keywords and major Medical Subject Heading (MeSH) keywords in PubMed (MEDLINE), PubMed Central, Google Scholar, Science Direct, and Cochrane Library for articles related to this topic and published between 2013 and 2023, up to April 18, 2023. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias, and 13 articles were finalized to be used in this review. The chosen articles included five cross-sectional studies, six systematic reviews and meta-analyses, and two literature reviews. This review provides strong evidence of the usage of microRNA for early diagnosis. It can also be used to exclude differential diagnoses of other diseases, and its prognostic value for determining metastasis and therapeutic efficacy in PC patients. Also, combining microRNA panels with carbohydrate antigen 19.9 (CA19-9) improves the sensitivity and specificity of microRNA as a biomarker.

Target-Induced Stepwise Disintegration of Starlike Branched and Multiplex Embedded Systems for Amplified Detection of Serum MicroRNA.

DNA nanotechnology has shown great promise for biosensing and molecular recognition. However, the practical application of conventional DNA biosensors is constrained by inadequate target stimuli, intricate design schemes, multicomponent systems, and susceptibility to nuclease degradation. To overcome these limitations, we present a class of starlike branched and multiplex embedded system (SBES) with an integrated functional design and cascade exponential amplification for serum microRNA (miRNA) detection. The DNA arms can be integrated into an all-in-one system by surrounding a branch point, with each arm endowed with specific functionalities by embedding different DNA fragments. These fragments include a segment complementary to the target miRNA for the recognition element, palindromic tails for self-primed polymerization, and a region with the same sequences as the target serving as the target analogue. Upon exposure to a target miRNA, the DNA arms unwind in a stepwise manner through palindrome-mediated dimerization and polymerization. This enables target recycling for subsequent reactions while releasing the target analogue to generate a secondary response in a feedback manner. A comparative analysis illustrates that the signal-to-noise ratio (SNR) of a full SBES with a feedback strategy is approximately 250% higher than the system without a feedback design. We demonstrate that the four-arm 4pSBES has the benefits of multifunctional integration, enhanced sensitivity, and low false-positive signals, which makes this approach ideally suited for clinical diagnosis. Moreover, an upgraded SBES with additional DNA arms (e.g., 6pSBES) can be constructed to allow multifunctional extension, offering unprecedented opportunities to build versatile DNA nanostructures for biosensing.

A mutation-sensitive, multiplexed and amplification-free detection of nucleic acids by stretching single-molecule tandem hairpin probes.

The detection of nucleic acid sequences in parallel with the discrimination of single nucleotide variations (SNVs) is critical for research and clinical applications. A few limitations make the detection technically challenging, such as too small variation in probe-hybridization energy caused by SNVs, the non-specific amplification of false nucleic acid fragments and the few options of dyes limited by spectral overlaps. To circumvent these limitations, we developed a single-molecule nucleic acid detection assay without amplification or fluorescence termed THREF (hybridization-induced tandem DNA hairpin refolding failure) based on multiplexed magnetic tweezers. THREF can detect DNA and RNA sequences at femtomolar concentrations within 30 min, monitor multiple probes in parallel, quantify the expression level of miR-122 in patient tissues, discriminate SNVs including the hard-to-detect G-U or T-G wobble mutations and reuse the probes to save the cost. In our demonstrative detections using mock clinic samples, we profiled the let-7 family microRNAs in serum and genotyped SARS-CoV-2 strains in saliva. Overall, the THREF assay can discriminate SNVs with the advantages of high sensitivity, ultra-specificity, multiplexing, reusability, sample hands-free and robustness.

MiR-148b inhibits M2 polarization of LPS-stimulated macrophages by targeting DcR3

Objective: To investigate the effect of microRNA (miR-148b) targeting decoy receptor 3 (DcR3) on macrophage polarization in sepsis. Methods: Experimental study. From December 2019 to December 2022, serum microRNA expression was detected in 3 patients with sepsis and 3 healthy controls in the clinical laboratory of Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Phorbol 12-myristate 13-acetate (PMA) was used to induce the differentiation of human acute monocytic leukemia cells THP-1 into macrophages, and then lipopolysaccharide (LPS) was added to stimulate the establishment of a sepsis cell model, and the expression changes of miR-148b and DcR3 were detected by RT-PCR and Western blot. Overexpression of DcR3 was used to detect the expression levels of TNF-α, CD163 and IL-10 in macrophages stimulated by LPS (100 ng/ml). Overexpression of miR-148b was used to observe the changes of molecular markers of macrophage polarization. The targeting regulation effect of miR-148b on DcR3 was determined by dual-luciferase reporter assay. t test was used to analyze whether there were statistical differences among the groups. Results: The expression of miR-148b was down-regulated (P<0.05) and the expression of DcR3 was up-regulated (P<0.01) in THP-1 macrophages stimulated by LPS. Overexpression of DcR3 inhibited the expression of TNF-α (P<0.05) and promoted the expression of CD163 (P<0.01) and IL-10 (P<0.01). When miR-148b mimics was added, the opposite effect was observed. The dual-luciferase reporter assay confirmed that miR-148b targets and binds to DcR3, inhibiting its transcription and expression. The results of flow cytometry showed that DcR3 could reverse the promoting effect of miR-148b on the CD86/CD163 ratio of macrophages (P<0.05). Conclusion: miR-148b inhibits the expression of DcR3, thereby inhibiting M2 polarization in LPS-stimulated macrophage cells.

Predictive miRNAs Patterns in Blood of Breast Cancer Patients Demonstrating Resistance Towards Neoadjuvant Chemotherapy.

The effect of chemotherapy in patients with breast cancer (BC) is uncertain. This study attempted to analyze serum microRNAs (miRNAs) in NAC resistant and sensitive BC patients and develop a miRNA-based nomogram model. To further help clinicians make treatment decisions for hormone receptor-positive patients. A total of 110 BC patients with NAC were recruited and assigned in sensitive and resistant group, and 4 sensitive patients and 3 resistant patients were subjected to high-throughput sequencing. The functions of their target genes were analyzed by GO and KEGG. Five BC-related reported miRNAs were selected for expression pattern measurement by RT-qPCR and multivariate logistic analysis. The nomogram model was developed using R 4.0.1, and its predictive efficacy, consistency and clinical application value in development and validation groups were evaluated using ROC, calibration and decision curves. There were 44 differentially-expressed miRNAs in resistant BC patients. miR-3646, miR-4741, miR-6730-3p, miR-6831-5p and miR-8485 were candidate for resistance diagnosis in BC. Logistic multiple regression analysis showed that miR-4741 (or = 0.30, 95% CI = 0.08-0.63, P = 0.02) and miR-6831-5p (or = 0.48, 95% CI = 0.24-0.78, P = 0.01) were protective factors of BC resistance. The ROC curves showed a sensitivity of 0.884 and 0.750 for miR-4741 and miR-6831-5P as markers of resistance, suggesting that they can be used as independent risk factors for BC resistance. The other 3 miRNAs can be used as calibration factors to establish the risk prediction model of resistance in BC. In risk model, the prediction accuracy of resistance of BC is about 78%. 5-miRNA signature diagnostic models can help clinicians provide personalized treatment for NAC resistance BC patients to improve patient survival. MiR-4741 and miR-6831-5p are independent risk factors for breast cancer resistance. This study constructed a nomogram model of NAC resistance in BC based on 5 differentially-expressed serum miRNAs.

Microarray profiling of serum micro-RNAs in women with Chlamydia trachomatis-associated recurrent spontaneous abortion: A case control study

Chlamydia trachomatis infection is a major cause of sexually transmitted diseases and adverse pregnancy outcomes such as recurrent spontaneous abortion (RSA). Micro-RNAs (miRNAs) have been known to be upregulated/downregulated in various reproductive-associated diseases such as ectopic pregnancy, preterm birth and pre-eclampsia. However, there is paucity of literature on miRNA profile in C. trachomatis-infected RSA. The present study aimed to determine the profile of serum miRNAs followed by their validation in C. trachomatis-infected RSA and to find target genes involved in biological pathways. Non-heparinized blood and first void urine were collected from 30 non-pregnant women with RSA and 30 non-pregnant women with ≥2 successful deliveries (controls) attending Department of Obstetrics and Gynaecology, Safdarjung hospital, New Delhi, India. C. trachomatis detection was done in urine by PCR and chlamydial load was determined by quantitative real-time PCR (qRT-PCR). miRNA expression was studied by microarray analysis followed by in vitro validation by qRT-PCR. Analysis of target genes/pathways was characterized in silico. 06 RSA patients were infected with C. trachomatis, while chlamydial load was found to be 6000–12,000 copies/ml. 110 circulating miRNAs were expressed differentially in infected RSA patients compared with controls. Of these, 16 were overexpressed and 94 downregulated. 06 differentially expressed circulating miRNAs were selected to validate the microarray results. qRT-PCR data confirmed the reliability of the microarray results: miR-4443, -5100, −7975 showed statistically significant upregulation, while miR-6808–5p, −3148, -6727–5p were significantly downregulated in infected RSA patients versus controls. Chlamydial load was positively correlated with these upregulated miRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that target genes of miRNAs in RSA are involved in AMPK, Akt and mTOR signaling pathways. Overall results indicate that differentially expressed circulating miRNAs are involved in pathogenesis of C. trachomatis-associated RSA and have the potential to be used as biomarkers for predicting RSA.

Male Infertility and the Risk of Developing Testicular Cancer: A Critical Contemporary Literature Review.

Background and Objectives: The relationship between male infertility (MI) and testicular cancer (TC) is bilateral. On one hand, it is well-established that patients diagnosed with TC have a high risk of pre- and post-treatment infertility. On the other hand, the risk of developing TC in male infertile patients is not clearly defined. The objective of this review is to analyze the histopathological, etiological, and epidemiological associations between MI and the risk of developing testicular cancer. This review aims to provide further insights and offer a guide for assessing the risk factors for TC in infertile men. Materials and Methods: A comprehensive literature search was conducted to identify relevant studies discussing the relationship between MI and the risk of developing TC. Results: The incidence rates of germ cell neoplasia in situ (GCNIS) appear to be high in infertile men, particularly in those with low sperm counts. Most epidemiological studies have found a statistically significant risk of developing TC among infertile men compared to the general or fertile male populations. The concept of Testicular Dysgenesis Syndrome provides an explanatory model for the common etiology of MI, TC, cryptorchidism, and hypospadias. Clinical findings such as a history of cryptorchidism could increase the risk of developing TC in infertile men. Scrotal ultrasound evaluation for testis lesions and microlithiasis is important in infertile men. Sperm analysis parameters can be useful in assessing the risk of TC among infertile men. In the future, sperm and serum microRNAs (miRNAs) may be utilized for the non-invasive early diagnosis of TC and GCNIS in infertile men. Conclusions: MI is indeed a risk factor for developing testicular cancer, as demonstrated by various studies. All infertile men should undergo a risk assessment using clinical examination, ultrasound, and semen parameters to evaluate their risk of TC.

Role of serum and salivary microRNAs as diagnostic biomarkers in gastric cancer

Introduction: Incidence of Gastric cancer (GC) is increasing alarmingly in the recent past due to changing lifestyle and diet pattern. GC usually has poor prognosis due to delayed diagnosis. Salivary and serum biomarkers are a potential early diagnostic tool for GC. MicroRNAs are promising biomarkers due to their stability in these body fluids and their pivotal role in carcinogenesis. This study helps to determine the role of serum and salivary microRNAs as diagnostic biomarkers in gastric cancer. Materials and Methods: The systematic review was performed as per the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The population, intervention, comparison, outcomes, and study (PICOS) framework was used as a strategy for this review. The data were retrieved from online databases such as Medline (PubMed), Web of Science, Scopus, and SpringerLink. Risk of bias and applicability concerns were evaluated using the four domains of QUADAS-2: patient selection, index test, reference standard, procedure and timing. Results: Quality evaluation based on diagnostic accuracy revealed that five studies conducted by Hou et al., Jianhong et al., Kaczor-Urbanowicz et al., Saliminejad et al., and So JBY et al. had the lowest risk of bias, according to a risk of bias chart created using Revman 5.4.1 software. A serum 12-miRNA biomarker assay was validated by the low risk of bias research. Conclusion: This systematic review provides an insight into the possible role and application of an array of miRNAs from various body fluids as a biomarker for the early detection of gastric cancer. The serum 12-miRNA biomarker assay, validated by a low risk of bias research can serve as a potential diagnostic tool to detect gastric cancer. However, the validation of other salivary, serum, and plasma miRNAs as a diagnostic biomarker for gastric cancer mandates further long-term follow-up studies in diverse ethnicity of populations.

Regulatory Roles of MicroRNAs in the Pathogenesis of Metabolic Syndrome.

Metabolic syndrome refers to a group of several disease conditions together with high glucose triglyceride levels, high blood pressure, lower high-density lipoprotein level, and large waist circumference. About 400 million people worldwide, one-third of the Euro-American population and 27% Chinese population over age 50 have it. microRNAs, an abundant novel class of endogenous small, non-coding RNAs in eukaryotic cells, act as negative controllers of gene expression by promoting either degradation/translational repression of target messenger RNA. More than 2000 microRNAs in the human genome have been identified and they are implicated in various biological & pathophysiological processes, including glucose homeostasis, inflammatory response, and angiogenesis. Destruction of microRNAs has a crucial role in the pathogenesis of obesity, cardiovascular disease, and diabetes. Recently the discovery of circulating microRNAs in human serum may help to promote metabolic crosstalk between organs and serves as a novel approach for the identification of various diseases, like Type 2 diabetes & atherosclerosis. In this review, we will discuss the most recent and up-to-date research on the pathophysiology and histopathology of metabolic syndrome besides their historical background and epidemiological highlight. As well as search the methodologies employed in this field of research and the potential role of microRNAs as novel biomarkers and therapeutic targets for metabolic syndrome in the human body. Furthermore, the significance of microRNAs in promising strategies, like stem cell therapy, which holds enormous promise for regenerative medicine in the treatment of metabolic disorders will also be discussed.

Evaluation of MicroRNAs in Pediatric Epilepsy.

The pathophysiology of epilepsy remains unknown. Recent research has shown that microRNA expression changes in epileptic adults. In the present work, we aimed to identify serum microRNA expression in drug-responsive and resistant children with idiopathic general- ized epilepsy. The study included 43 (20 male and 23 female) epilepsy patients and 66 (43 male and 23 female) control subjects. The mean ages of the groups were 113.41 ± 61.83 and 105.46 ± 62.31 months, respectively. Twenty-eight epileptic patients were classi- fied as drug resistant. Thirteen of the controls were the siblings of patients with epilepsy. The study only included children with idiopathic generalized epilepsy who had normal brain mag- netic resonance imaging. The serum microRNA expressions (microRNA-181a, microRNA-155, microRNA-146, and microRNA-223) were investigated. Expressions of serum microRNA-181a, microRNA-155, microRNA-146, and microRNA-223 were previously investigated in epilepsy patients and children with febrile seizures. Therefore, these microRNAs were chosen. The expressions of serum levels of microRNAs were determined using quantitative real-time poly- merase chain reaction. The results indicated that the expressions of serum microRNA-155 and microRNA-223 were elevated in epileptic children (P < .05). The expression of the same microRNAs was also elevated in individuals with drug-resistant epilepsy compared to healthy controls (P < .05). microRNA-146a, microRNA-155, and microRNA-223 expressions were higher in drug-resistant patients than in drug-responsive children (P < .05). A logistic regression study determined that an increase of microRNA-155 was a risk for epilepsy, while a decrease of microRNA-146a risk for epilepsy. Few researchers have investigated the function of microRNAs in the develop- ment of childhood epilepsy. Our findings revealed that epilepsy patients have abnormal microRNAexpression.

Urinary microRNA profiling in pregnant women identifies placental microRNAs that are candidate biomarkers for monitoring placental health.

MicroRNAs are among the key modulators of placental transcriptome dynamics. This study aimed at comparative profiling of urinary (sampling at 228-230 gestational days, g.days), serum (217-230 g.days), and placental (279-286 g.days) microRNAs in three healthy pregnant women using miRNome sequencing. Placenta showed significant enrichment of microRNAs compared with serum and urine (1174, 341, and 193, respectively; P < 10-5 ). All sample types shared 153 microRNAs, representing candidate biomarkers for placental health. Urine samples contained eight of 56 transcripts from the placenta-specific chromosome 19 microRNA cluster C19MC and one of 91 transcripts (miR-432-5p) from the chromosome 14 cluster C14MC. These data suggest an active filtering at the maternal-fetal interface in passing through only selected microRNAs. Urine represents a valid source to monitor the signature of placenta-expressed microRNAs that are differentially expressed in pregnancy complications.

Identification and evaluation of a reliable, non-invasive diagnostic method using serum microRNA expression to diagnose high-risk colorectal cancer candidates.

e15519 Background: Screening is of paramount importance in early colorectal cancer detection which can significantly reduce its mortality. This study aims to identify a non-invasive diagnostic method using serum microRNA expression to diagnose colorectal cancer patients. Methods: Serum samples were prospectively collected from CRC patients or normal subjects during 2017 to 2021 in Queen Mary Hospital of Hong Kong and divided into 3 study cohorts: Training cohort (n = 129 per group), Validation cohort (n = 200 per group) and Prediction cohort (n = 260). Quantitative PCR was applied to detect the serum level of 20 candidate microRNAs. Multiple linear regression was used to formulate a serum microRNA panel for diagnosing CRC patients. The performance was evaluated by ROC analysis. The cost-effectiveness was investigating by comparing the cost of two CRC diagnostic strategies comprising of (i) colonoscopy alone and (ii) microRNA panel and followed by colonoscopy strategies to microRNA panel tested positive patients. Results: The values of 3 pairs of serum microRNAs, including miR-106b/miR-1246, miR-106b/miR-16 and miR-106b/miR-21 showed statistical significant difference between CRC patients and normal subjects. A serum microRNA panel formulated from these 3 pairs of microRNAs was able to diagnose CRC patients from normal subjects with high accuracy for both training cohort [AUC: 0.9078 (95% CI, 0.9122 To 0.9734; p &lt; 0.0001)] and Validation cohort (AUC: 0.8904), suggesting that this microRNA panel had a consistent performance across different patient cohorts. Our prediction cohort showed that this microRNA panel was able to screen CRC patients with 85.8% sensitivity, 80.95% specificity, 86.9% positive predictive value and 79.4% negative predictive value. Cost-effectiveness analysis revealed that the strategy of combining serum miRNA test and colonoscopy was a more cost-effective approach compared to colonoscopy alone. The average cost saved per patient was around HK$4010. Conclusions: The serum miRNA test was a feasible, promising and cost-effective non-invasive biomarker for diagnosing CRC patients from normal subjects.

Evaluation of microRNA expression levels during the craving period of patients diagnosed with severe alcohol use disorder

ABSTRACT Background The aim of this study is to compare the serum MicroRNA (miRNA) expression levels on the first day of hospitalization and at the end of the first month of treatment in patients with alcohol use disorder and severe craving symptoms. Through the obtained data, biological agents targeting microRNA for alcohol craving may be developed. Methods The volunteer group consists of four patients diagnosed with severe alcohol use disorder. Sociodemographic and Clinical Information Form, DSM-5 Structured Clinical Interview-Clinical Version (SCID-5-CV), Penn Alcohol Craving Scale (PACS) were used as clinical assessment tools. Peripheral blood samples were obtained at the time of application and on the 30th day. miRNA isolation was performed. The expression levels of 2578 different mature human miRNAs were measured. Results The miRNAs showing statistically significant differences in peripheral blood samples taken on the 1st and 30th days from alcohol users are as follows: miR-19a-3p, miR-6849-5p, miR-6726-5p, miR-6848-5p, miR-186-5p, miR-6889-5p, miR-933, miR-370-3p, miR-5739, miR-103a-2-5p, miR-6860, miR-1254, miR-1260a, miR-3921, miR-127-3p, miR-8064, miR-6870-5p, miR-4688 Conclusions A significant difference was found between the 1st and 30th days in 18 of 2578 miRNAs scanned. It is aimed to investigate these 18 miRNAs in larger sample groups during the alcohol craving period.

Serum microRNA Levels as a Biomarker for Diagnosing Non-Alcoholic Fatty Liver Disease in Chinese Colorectal Polyp Patients.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374, p = 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978, p = 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081, p = 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582, p = 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (p = 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (p < 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.

Expression of microRNAs in leukocytes and serum of asbestosis patients

BackgroundAlthough asbestos use is banned in many countries, long latency of asbestos-related diseases like pleural plaques or asbestosis mean it is still a public health issue. People suffering from these diseases have a higher risk of developing mesothelioma or lung cancer, which can progress quickly and aggressively. MicroRNAs were suggested as potential biomarkers in several diseases. However, in asbestosis, blood microRNAs are less explored. Since miR-32-5p, miR-143-3p, miR-145-5p, miR-146b-5p, miR-204-5p and miR-451a are involved in fibrotic processes and in cancer, expression of these microRNAs was analyzed in leukocytes and serum of asbestosis patients.MethodsMicroRNA expression was analyzed in leukocytes and serum of 36 patients (26 affected by pleural plaques and 10 by asbestosis) and 15 healthy controls by real-time RT-PCR. Additionally, data analyses were performed regarding disease severity based on ILO classification.ResultsMicroRNA miR-146b-5p was significantly down-regulated in leukocytes of patients suffering from pleural plaques with a large effect indicated by η2p = 0.150 and Cohen’s f = 0.42, a value of difference of 0.725 and a 95% confidence interval of 0.070–1.381. In patients suffering from asbestosis miR-146b-5p was not significantly regulated. However, data analyses considering disease severity only, revealed that miR-146b-5p was significantly down-regulated in leukocytes of mildly diseased patients compared to controls with a large effect indicated by η2p = 0.178 and Cohen’s f = 0.465, a value of difference of 0.848 and a 95% confidence interval of 0.097–1.599. Receiver operating characteristic (ROC) curve and an area under the ROC curve value of 0.757 for miR-146b-5p indicated acceptable discrimination ability between patients suffering from pleural plaques and healthy controls. Less microRNAs were detectable in serum than in leukocytes, showing no significant expression differences in all participants of this study. Moreover, miR-145-5p was regulated significantly differently in leukocytes and serum. An R2 value of 0.004 for miR-145-5p indicated no correlation in microRNA expression between leukocytes and serum.ConclusionLeukocytes seem more suitable than serum for microRNA analyses regarding disease and potentially cancer risk assessment of patients suffering from asbestos-related pleural plaques or asbestosis. Long-term studies may reveal whether down-regulation of miR-146b-5p in leukocytes might be an early indicator for an increased cancer risk.

The association between selected serum microRNAs, adipokine concentrations, and body composition assessed with dual-energy X-ray absorptiometry in young women with polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Combined measurement of circulating tumor cells and magnetic nanoparticles-assisted multiple blood markers improves the diagnostic efficiency of early-stage lung adenocarcinoma

The study aims to evaluate the efficiency and clinical value of circulating tumor cells (CTCs), blood tumor markers, and serum microRNAs for diagnosing lung adenocarcinoma in its early stages. The study included 40 patients with early-stage lung adenocarcinoma, 40 individuals with benign pulmonary nodules, and 40 healthy volunteers in groups 1, 2, and 3, respectively. The negative enrichment–fluorescence in situ hybridization was used to classify and quantify the aneuploidy and its number distribution in CTCs in groups 1–3. Magnetic nanoparticles were used to extract DNA. The levels of miR-223-3p and miR-486-5p in the serum of groups 1–3 were then determined using reverse transcription quantitative real-time polymerase chain reaction. CTC aneuploidy and its number distribution was detected and the detection of various blood markers was performed. The diagnostic accuracy was determined through receiver operating characteristic curve (ROC) drawn among the groups. The total number of CTCs and aneuploidies in patients with early-stage lung adenocarcinoma was higher than in patients with benign pulmonary nodules and healthy people. Patients with early-stage lung adenocarcinoma had significantly higher levels of miR-223-3p and miR-486-5p than patients with benign pulmonary nodules and healthy people. ROC analysis found that the sensitivity and area under the ROC curve of CTCs combined with multiple blood markers for distinguishing patients with early-stage lung adenocarcinoma from those without lung nodules were 80.12% and 0.945%, respectively. The sensitivity and area under the ROC curve of the patients were 85.38% and 0.948%, respectively. The detection of CTCs, carcinoembryonic antigen, cytokeratin 19 fragment, miR-223-3p, and miR-486-5p was effective for early-stage lung adenocarcinoma and benign lung nodules. The diagnosis of miR-223-3p is clinically significant, as the accurate diagnostic index of miR-223-3p is better than that of CTCs and other blood indicators. However, CTCs combined with blood markers have the highest efficiency in diagnosing early-stage lung adenocarcinoma.

Circulating microRNAs in migraine patients: Systematic review and bioinformatic analysis. (P8-12.012)

<h3>Objective:</h3> To identify differentially regulated microRNAs between patients with and without migraine. <h3>Background:</h3> Migraine is a common neurological disorder with a high burden of disease. For some years, there has been significant interest in searching for biomarkers that can help diagnose, stratify, and discover new therapies. MicroRNAs are proposed as potential diagnostic biomarkers that can support already established clinical criteria. <h3>Design/Methods:</h3> A systematic search was performed using four databases. Searches were performed using MeSH terms and keywords until August 2021. We included studies that evaluated circulating microRNAs in blood or serum of people with migraine, with no restrictions on age, race, or gender. A narrative synthesis of the findings of the included studies and a summary of deregulated microRNAs in the context of migraine were provided. Functional characterization of microRNAs was performed using DIANA-miRPath v3.0 software, using the KEGG database. In the end, metabolic pathway junctions were searched, and significant up- and down-regulated RNAs were selected. <h3>Results:</h3> In total, 40 circulating microRNAs were identified deregulated with a statistically significant p-value. However, only miR-34a-5p and miR-375 were found to be up-regulated in more than one article. Of the 40 microRNAs, we found 34 up-regulated and 6 down-regulated, no microRNAs were identified deregulated in both directions. The bioinformatic analysis showed the signaling pathways most closely related to the microRNAs studied were the graded acid biosynthesis pathway, the prion disease pathway, and the hippopotamus signaling lifetime. <h3>Conclusions:</h3> Altered levels of microRNAs in human biofluids, specifically in serum and blood, can be used as a potential biomarker in the diagnosis of migraine and differentiation from other types of headache, as well as potentially useful as a marker for follow-up or as a target for treatment; however, further studies are still required. <b>Disclosure:</b> Dr. Cardenas Cruz has nothing to disclose. Dr. Aguilera Peña has nothing to disclose. Dr. García Alfonso has nothing to disclose.