scholarly journals Maternal Circulating Exosomal miRNAs as Non-invasive Biomarkers for the Prediction of Fetal Ventricular Septal Defect

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuxia Jin ◽  
Ling Ai ◽  
Xiaojun Chai ◽  
Ping Tang ◽  
Weihua Zhang ◽  
...  

Objective: This study aimed to identify maternal circulating exosomal miRNAs as potential non-invasive biomarkers for the early detection of fetal ventricular septal defects (VSDs).Methods: In total, 182 pregnant women, comprising 91 VSD cases and 91 matched controls, were included in this study. Exosomes were isolated; dysregulated exosomal miRNAs were profiled using next-generation sequencing. Differential abundance of miRNAs was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic accuracy was evaluated by constructing receiver operating characteristic (ROC) curves.Results: In total, 77 serum exosomal miRNAs were found to be differentially expressed in the VSD group compared to their expression in the control group. Among these, five downregulated exosomal miRNAs were validated using qRT-PCR. hsa-miR-146a-5p was identified to be capable of distinguishing VSD cases from controls (area under the ROC curve [AUC]: 0.997; p < 1.00E-05).Conclusion: Circulating exosomal miRNAs, particularly hsa-miR-146a-5p, may be predictive biomarkers for the non-invasive prenatal diagnosis of fetal VSDs.

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Rasa Liutkeviciene ◽  
Alvita Vilkeviciute ◽  
Greta Morkunaite ◽  
Brigita Glebauskiene ◽  
Loresa Kriauciuniene

Abstract Background Our purpose was to determine if SIRT1 (rs4746720, rs3740051) genotypes have an influence on the development of pituitary adenoma (PA). Methods The study group included 142 patients with pituitary adenoma (PA) and the control group consisted of 826 healthy people. The genotyping of SIRT1 (rs4746720, rs3740051) was carried out using the real-time polymerase chain reaction method. Results Statistically significant results were obtained in the analysis of SIRT1 rs3740051. Significant differences in genotype (G/G, G/A, A/A) distribution were obtained comparing patients with PA without recurrence and PA with recurrence (0, 17.9, 82.1% vs. 6.7, 6.7, 86.7%, respectively, p = 0.022). Also, statistically significant differences were observed when comparing the genotype (G/G, G/A, A/A) distribution in the non-invasive PA group and the invasive PA group (3.4, 25.9, 70.7% vs. 0, 8.3, 91.7%, respectively, p = 0.003), and allele G was less frequently observed in invasive PA, than in non-invasive PA (4.2% vs. 16.4%, p < 0,001). Further analysis revealed that G/A (OR = 0.261; 95% CI:0.099–0.689; p = 0.007) and each allele A (OR = 0.229; 95% CI:0.091–0.575; p = 0.002) were associated with lower odds of occurring an invasive PA. Conclusions Our study revealed that SIRT1 rs3740051 is associated with PA recurrence and invasiveness. The haplotype containing alleles C-A in rs12778366-rs3740051 was found to be associated with increased odds of PA development as well.


2020 ◽  
Vol 7 (3) ◽  
pp. e703 ◽  
Author(s):  
Kristoffer E. Leon ◽  
Ryan D. Schubert ◽  
Didac Casas-Alba ◽  
Isobel A. Hawes ◽  
Prashanth S. Ramachandran ◽  
...  

ObjectiveIn 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization.MethodsRNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA.ResultsmNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject.ConclusionmNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dao-xiong Ye ◽  
Si-si Wang ◽  
Ying Huang ◽  
Pan Chi

Abstract Background Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.


Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1350-1355
Author(s):  
Naihua Liu ◽  
Yuancheng Huang ◽  
Fengbin Liu ◽  
Hong Liu

Abstract Objective The aim of this study was to integrate the serum exosomal miRNA miR-122-5p with canonical serological biomarkers for the non-invasive screening of chronic atrophic gastritis (CAG) patients. Methods miR-122-5p and U6 were amplified by the quantitative reverse transcription polymerase chain reaction (RT-qPCR), gastrin (GAS), pepsinogen I (PG-I), and PG-II and were measured by ELISA. The area under the receiver operating characteristic (ROC) curves and their correlation were analyzed. Results In the present study, GAS level and PG-I/PG-II ratio (PGR) were increased in CAG group, but there was no significant difference in PG-I or PG-II levels between CAG group and chronic non-atrophic gastritis (CNAG) group. Only GAS level and PG-I/PG-II ratio were significantly correlated with atrophy, and not any other clinicopathologic factors. Expression of hsa-miR-122-5p positively correlated with GAS level, PG-I level, and PGR, while it negatively correlated with PG-II level; however, none of them had significant difference. The combination of GAS, PGR, and hsa-miR-122-5p presented as a better model for non-invasive screening of CAG compared to others. Conclusion These results suggested that serum exosomal hsa-miR-122-5p combined with GAS and PGR would elevate accuracy and specificity in non-invasive screening of CAG.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5218 ◽  
Author(s):  
Yu-Long Wang ◽  
Wen Yu

Objective MicroRNA (miR)-122 is highly expressed in the liver, where it has been implicated as a regulator of fatty-acid metabolism. A recent study reported that miR-122 plays a role in pathogenesis of atherosclerosis; however, whether it connects with severity of atherosclerotic lesion is still controversial. We therefore investigated the association between miR-122 expression and presence and severity of coronary atherosclerotic plaque. Methods During January–November 2017, we included 300 patients with coronary heart disease (CHD) and 100 subjects as the control group. MiR-122 content was detected by quantitative real-time polymerase chain reaction. MiR-122 level was identified in all subjects, and the Spearman correlation between miR-122 and severity of atherosclerosis was analyzed. Results Patients with CHD had higher miR-122 expression than in control group (2.61, 0.91–8.86 vs. 1.62, 0.71–3.45, p < 0.001). Gensini score was significantly associated with miR-122 expression (r = 0.7964, p < 0.001). The odds ratio of miR-122 solely was 0.12 (95% CI [0.05–0.43]) and factors such as cholesterol, triglyceride together with miR-122 level were closely associated with atherosclerosis (all p < 0.001). Conclusions The serum level of miR-122 may be used to differentiate between mild and severe coronary atherosclerotic lesion. Use of this marker might allow non-invasive diagnosis the degree of coronary atherosclerosis.


2018 ◽  
Vol 51 (6) ◽  
pp. 2704-2715 ◽  
Author(s):  
Dongzhi Hu ◽  
Yang Zhan ◽  
Kegan Zhu ◽  
Ming Bai ◽  
Jiayi Han ◽  
...  

Background/Aims: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths worldwide. Thus, methods for early diagnosis of CRC are urgently needed. We aimed to identify potential long non-coding RNAs (lncRNAs) in circulatory exosomes that may serve as biomarkers for the detection of early-stage CRC. Methods: Exosomes from the plasma of CRC patients (n = 50) and healthy individuals (n = 50) were isolated by ultracentrifugation, followed by extraction of total exosomal RNAs using TRIzol reagent. Microarray analysis was used for exosomal lncRNA profiling in the two groups, and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression level of lncRNAs in all patients and healthy subjects. Results: The expression of six lncRNAs (LNCV6_116109, LNCV6_98390, LNCV6_38772, LNCV_108266, LNCV6_84003, and LNCV6_98602) was found to be significantly up-regulated in CRC patients compared with that in healthy individuals by qRT-PCR. The receiver operating characteristic curve was used to verify their diagnostic accuracy. The values of the area under the curve for these lncRNAs were 0.770 (LNCV6_116109), 0.7500 (LNCV6_98390), 0.6500 (LNCV6_38772), 0.6900 (LNCV_108266), 0.7500 (LNCV6_84003), and 0.7200 (LNCV6_98602). Conclusion: Our study suggested that the expression of these six exosomal lncRNAs (LNCV6_116109, LNCV6_98390, LNCV6_38772, LNCV_108266, LNCV6_84003, and LNCV6_98602) was significantly up-regulated in the plasma of CRC patients, and that they may serve as potential non-invasive biomarkers for early diagnosis of CRC.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Lanhua Kang ◽  
Ning Li ◽  
Lexiu Wang

Background. This study is aimed at exploring the significance of the expression of miR-23a and miR-146a in patients with periodontitis and their correlations with inflammatory factors. Methods. A total of 120 patients with chronic periodontitis admitted to the department of stomatology in Yantai Yuhuangding Hospital from August 2017 to December 2018 were enrolled as a study group, and 80 healthy volunteers in physical examination during the same period were enrolled as a control group. The expression of miR-23a, miR-146a, interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) in the saliva of people in the two groups was determined using the quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results. The study group showed significantly higher relative expression of saliva miR-23a and miR-146a than the control group. The area under the curve (AUC) of saliva miR-23a and miR-146a for diagnosing periodontitis was 0.857 and 0.886, respectively. The expression of saliva miR-23a and miR-146a increased with the deterioration of periodontitis in the patients. After basic treatment, the study group showed significantly decreased expression of saliva miR-23a and miR-146a. Patients in the study group showed significantly higher levels of saliva IL-1β, IL-6, and IL-17 than those in the control group, and their saliva miR-23a and miR-146a were positively correlated with their saliva IL-1β, IL-6, and IL-17, respectively. Conclusion. Saliva miR-23a and miR-146a can be used as biomarkers for the diagnosis and assessment of periodontitis, and they may have regulatory relationships with IL-1β, IL-6, and IL-17.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Na Shi ◽  
Lihui Deng ◽  
Weiwei Chen ◽  
Xiaoxin Zhang ◽  
Ruijie Luo ◽  
...  

Background and Aims. The aim of this study was to determine the expression of microRNA-127 (miR-127) in both rat models and patients of acute pancreatitis (AP) with lung injury (LI). Methods. Rats were administrated with retrograde cholangiopancreatography injection of 0.5% or 3.5% sodium taurocholate to induce AP with mild or severe LI and were sacrificed at 6, 12, and 24 h. Rats from the control group received a laparotomy only. Plasma from a prospective cohort of AP patients was collected. The levels of miR-127 in the tissues and plasma were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results. The upregulation of miR-127 in the lungs of rats was detected in the groups of AP with severe LI at 6 h and 24 h, whereas it was scarcely detectable in plasma. In the pilot study that included 18 AP patients and 5 healthy volunteers, the plasma miR-127 level was significantly downregulated in AP patients with respiratory failure compared with the healthy volunteers (P=0.014) and those without respiratory failure (P=0.043). Conclusion. miR-127 might serve as a potential marker for the identification of AP with LI.


2020 ◽  
Vol 16 (1) ◽  
pp. 47-53
Author(s):  
Vicente Benavides-Córdoba ◽  
Mauricio Palacios Gómez

Introduction: Animal models have been used to understand the pathophysiology of pulmonary hypertension, to describe the mechanisms of action and to evaluate promising active ingredients. The monocrotaline-induced pulmonary hypertension model is the most used animal model. In this model, invasive and non-invasive hemodynamic variables that resemble human measurements have been used. Aim: To define if non-invasive variables can predict hemodynamic measures in the monocrotaline-induced pulmonary hypertension model. Materials and Methods: Twenty 6-week old male Wistar rats weighing between 250-300g from the bioterium of the Universidad del Valle (Cali - Colombia) were used in order to establish that the relationships between invasive and non-invasive variables are sustained in different conditions (healthy, hypertrophy and treated). The animals were organized into three groups, a control group who was given 0.9% saline solution subcutaneously (sc), a group with pulmonary hypertension induced with a single subcutaneous dose of Monocrotaline 30 mg/kg, and a group with pulmonary hypertension with 30 mg/kg of monocrotaline treated with Sildenafil. Right ventricle ejection fraction, heart rate, right ventricle systolic pressure and the extent of hypertrophy were measured. The functional relation between any two variables was evaluated by the Pearson correlation coefficient. Results: It was found that all correlations were statistically significant (p <0.01). The strongest correlation was the inverse one between the RVEF and the Fulton index (r = -0.82). The Fulton index also had a strong correlation with the RVSP (r = 0.79). The Pearson correlation coefficient between the RVEF and the RVSP was -0.81, meaning that the higher the systolic pressure in the right ventricle, the lower the ejection fraction value. Heart rate was significantly correlated to the other three variables studied, although with relatively low correlation. Conclusion: The correlations obtained in this study indicate that the parameters evaluated in the research related to experimental pulmonary hypertension correlate adequately and that the measurements that are currently made are adequate and consistent with each other, that is, they have good predictive capacity.


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