scholarly journals miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are Sensitive Biomarkers to Diagnose Sudden Cardiac Death

2021 ◽  
Author(s):  
Fengping Yan ◽  
Yuanyuan Chen ◽  
Xing Ye ◽  
Fu Zhang ◽  
Shiquan Wang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiac Death ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Pathological Changes ◽  
Diagnostic Challenge ◽  
Roc Curve Analysis ◽  
Injury Death ◽  
Diagnostic Biomarkers ◽  
Autopsy Findings

Abstract BackgroundSudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. MethodsThis study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as acute myocardial infarction (AMI) without positive autopsy findings and 16 as atherosclerotic cardiovascular diseases (ASCVD) with gross myocardial scar. Carbon monoxide (CO) intoxication (n=14) and fatal injury death (n=14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Resultsit showed that heart samples from the AMI group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, ROC curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71-97.06% and specificity of 70-100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the AMI heart as relative to ASCVD, and a combination of two miRNAs presented higher diagnostic value (AUC=0.7407-0.8667). ConclusionmiR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

scholarly journals miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are sensitive biomarkers to diagnose sudden cardiac death

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fengping Yan ◽  
Yuanyuan Chen ◽  
Xing Ye ◽  
Fu Zhang ◽  
Shiquan Wang ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Pathological Changes ◽  
Diagnostic Challenge ◽  
Roc Curve Analysis ◽  
Injury Death ◽  
Diagnostic Biomarkers ◽  
Autopsy Findings

Abstract Background Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. Methods This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Results It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71–97.06% and specificity of 70–100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407–0.8667). Conclusion miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

scholarly journals Expression of the Novel Cardiac Biomarkers sST2, GDF-15, suPAR, and H-FABP in HFpEF Patients Compared to ICM, DCM, and Controls

2020 ◽  
Vol 9 (4) ◽  
pp. 1130
Author(s):  
Peter Jirak ◽  
Rudin Pistulli ◽  
Michael Lichtenauer ◽  
Bernhard Wernly ◽  
Vera Paar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Biomarkers ◽  
Control Group ◽  
The Novel ◽  
Significant Elevation ◽  
Serum Samples ◽  
Diagnostic Challenge ◽  
Diagnostic Biomarkers ◽  
Diagnostic Potential ◽  
Cardiovascular Biomarkers

Background: Heart failure with preserved ejection fraction (HFpEF) remains an ongoing therapeutic and diagnostic challenge to date. In this study we aimed for an analysis of the diagnostic potential of four novel cardiovascular biomarkers, GDF-15, H-FABP, sST2, and suPAR in HFpEF patients compared to controls as well as ICM, and DCM. Methods: In total, we included 252 stable outpatients and controls (77 DCM, 62 ICM, 18 HFpEF, and 95 controls) in the present study. All patients were in a non-decompensated state and on a stable treatment regimen. Serum samples were obtained and analyzed for GDF-15 (inflammation, remodeling), H-FABP (ischemia and subclinical ischemia), sST2 (inflammation, remodeling) and suPAR (inflammation, remodeling) by means of ELISA. Results: A significant elevation of GDF-15 was found for all heart failure entities compared to controls (p < 0.005). Similarly, H-FABP evidenced a significant elevation in all heart failure entities compared to the control group (p < 0.0001). Levels of sST2 were significantly elevated in ICM and DCM patients compared to the control group and HFpEF patients (p < 0.0001). Regarding suPAR, a significant elevation in ICM and DCM patients compared to the control group (p < 0.0001) and HFpEF patients (p < 0.01) was observed. An AUC analysis identified H-FABP (0.792, 95% CI 0.713–0.870) and GDF-15 (0.787, 95% CI 0.696–0.878) as paramount diagnostic biomarkers for HFpEF patients. Conclusion: Based on their differences in secretion patterns, novel cardiovascular biomarkers might represent a promising diagnostic tool for HFpEF in the future.

scholarly journals Evaluation of Plasma MMP-9 and VEGF-A mRNAs as Non-invasive Diagnostic Biomarkers in Women with Endometriosis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Sepideh Abdollahi ◽  
Pantea Izadi ◽  
Shahla Noori Ardebili ◽  
Samaneh Chegeni ◽  
Mir Saead Yekaninejad
Keyword(s):  
Plasma Level ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Level ◽  
Control Group ◽  
P Value ◽  
Mrna Levels ◽  
Diagnostic Biomarker ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Significant Difference

Background: Endometriosis is one of the common gynecological diseases and can lead to pelvic pain, dysmenorrhea, dyspareunia, and infertility in women. Thus, accurate and early diagnosis is a pivotal issue and an essential need for managing this disorder. At the present, the gold standard diagnostic method for endometriosis is laparoscopic surgery that is an invasive method and can lead to delay in diagnosis. Thus, there is an immediate necessity to search for non-invasive diagnostic biomarkers, such as blood-based ones. Objectives: Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor-A (VEGF-A) have essential roles in the pathogenesis of endometriosis. Therefore, in this study, we evaluated the plasma mRNA levels of MMP-9 and VEGF-A, as potential non-invasive diagnostic biomarkers for endometriosis. Methods: This study included 48 women (24 cases and 24 controls) who underwent laparoscopy for suspected endometriosis. Preoperative plasma samples were collected, and after RNA extraction, the levels of MMP-9 and VEGF-A mRNAs were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: Plasma MMP-9 mRNA level was statistically higher in endometriosis patients compared with the control group (P value = 0.01). However, plasma VEGF-A mRNA level did not show a significant difference between the two groups (P value =0.5). Conclusions: It seems that the plasma level of MMP-9 mRNA in endometriosis patients is significantly higher than in non-endometriosis women. This finding can provide new insights regarding this mRNA’s applicability as a non-invasive diagnostic biomarker for discovering new cases of endometriosis (newly diagnosed). According to our results, despite the suggested role of VEGF-A in endometriosis pathogenesis, it seems that the plasma level of VEGF-A mRNA does not have the potential to be used as a non-invasive diagnostic biomarker.

scholarly journals Discrepancies between clinical and autopsy diagnosis of cause of death among psychiatric patients who died due to natural causes. A retrospective autopsy study

2019 ◽  
Vol 76 (3) ◽  
pp. 278-283
Author(s):  
Dragan Mitrovic ◽  
Ivana Savic ◽  
Radmila Jankovic
Keyword(s):  
Cardiovascular Diseases ◽  
Clinical Diagnosis ◽  
Cause Of Death ◽  
Causes Of Death ◽  
Psychiatric Patients ◽  
Psychiatric Hospitals ◽  
Control Group ◽  
Natural Death ◽  
Autopsy Findings ◽  
Somatic Diseases

Background/Aim. Autopsy studies rarely investigate the causes of natural death in psychiatric population. The aim of this study was to examine the causes of death among the subjects with various psychiatric disorders in whom a clinical (pathoanatomical) autopsy was requested. Methods. The study group included 118 patients (65% men, 35% women, mean age 58.2 ? 13.6 years) with a psychiatric diagnosis, in whom a clinical autopsy was performed. We compared the distribution of causes of natural death among psychiatric patients and other patients, representatives of the general population who died of natural causes. We also analyzed the difference between clinical diagnoses of cause of death and the autopsy findings in psychiatric patients. Results. Psychiatric patients died earlier than the control group (58 vs. 69 years), usually due to the respiratory (46%) and cardiovascular diseases (37%). The most common diagnoses in psychiatric patients were organic psychoses and dementias (F00-F09) and schizophrenia and schizoaffective disorders (F20-F29). Majority of the patients (55%) died in general hospitals vs. specialized psychiatric hospitals (45%) due to somatic diseases. There was a significant difference in the distribution of causes of death compared to the control group in which the cardiovascular diseases dominated. Even in 64% of psychiatric patients there was a discrepancy between the clinical diagnosis of the cause of death and definite autopsy findings. Conclusion. The assessment of somatic diseases in psychiatric patients is insufficient, especially in specialized psychiatric hospitals. That leads to a significant discrepancy between clinical diagnosis of the cause of death and autopsy findings. Therefore, it is necessary to pay additional attention in diagnostics and treatment of somatic diseases in these patients to improve their health care.

scholarly journals Differential Expression of miR-101 and miR-744 in Nasopharyngeal Carcinoma in Pahang State of Malaysia

2018 ◽  
Vol 16 (5) ◽  
pp. 295-306
Author(s):  
Azmir AHMAD ◽  
Haziq Abdul WAHID ◽  
Wan Ishlah LEMAN ◽  
Noor Syamila OTHMAN ◽  
Azlina Abdul RAHMAN ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Sample Size ◽  
Differential Expression ◽  
Control Group ◽  
Roc Curve Analysis ◽  
Diagnostic Biomarkers ◽  
Total Rna ◽  
Formalin Fixed Paraffin ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded

Previous study found that microRNA-101 (miR-101) and microRNA-744 (miR-744) were deregulated in head and neck cancers and were implicated in nasopharyngeal carcinoma (NPC) carcinogenesis. Thus, this study aimed to determine the expression of miR-101 and miR-744 in NPC and analyse the utility of these microRNAs (miRNAs) as diagnostic biomarkers. Total RNA was extracted from 31 NPC and 7 non-NPC control formalin-fixed paraffin-embedded (FFPE) samples. Complementary DNA (cDNA) was synthesized from the total RNA and proceeded with quantitative real-time polymerase chain reaction. Differential expression of miR-101 and miR-744 were calculated from quantification cycle (Cq) data using 2-ΔΔCq calculation. The performance of these miRNAs were calculated using receiver operating characteristic (ROC) curve analysis. The differential expression for miR-101 and miR-744 were -1.39 (p < 0.05) and 2.48 (p > 0.05), respectively, where the deregulations were consistent with the previous report. The area under curve for miR-101, miR-744 and combination of miR-101 and miR-744 were 0.654 (95 % CI: 0.465 - 0.844), 0.588 (95 % CI: 0.368 - 0.808) and 0.626 (95 % CI: 0.481 - 0.771), respectively. However, re-analysis using balanced sample size between NPC and non-NPC control group showed the value decreased to 0.653 (95 % CI: 0.347 - 0.959) for miR-101 but increased to 0.827 (95 % CI: 0.601 - 1.000) for miR-744 and 0.758 (95 % CI: 0.576 - 0.939) for the combination of miR-101 and miR-744, indicating the importance of having a balanced sample size. We have successfully determined the expression of miR-101 and miR-744 in NPC samples. We also demonstrated statistically the utility of these miRNAs as diagnostic biomarkers.

scholarly journals Circulating Exosomal miRNAs as Novel Biomarkers for Stable Coronary Artery Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ping Zhang ◽  
Tao Liang ◽  
Yao Chen ◽  
Xuan Wang ◽  
Tianlong Wu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
Protein Concentration ◽  
Stable Coronary Artery Disease ◽  
Control Group ◽  
Diagnostic Biomarkers ◽  
Exosomal Mirnas ◽  
Artery Disease ◽  
Serum Exosomes

Exosomal miRNAs are currently being explored as a novel class of biomarkers in cardiovascular diseases. However, few reports have focused on the value of circulating exosomal miRNAs as biomarkers for stable coronary artery disease (SCAD). Here, we aimed to investigate whether miRNAs involved in cardiovascular diseases in circulating exosomes could serve as novel diagnostic biomarkers for SCAD. Firstly, the serum exosomes were isolated and purified by the ExoQuick reagent and identified by transmission electron microscopy, western blot, and nanoparticle tracking analysis. Then, the purified exosomes were quantified by measuring the exosome protein concentration and calculating the total protein amount. Next, eight miRNAs involved in cardiovascular diseases, miR-192-5p, miR-148b-3p, miR-125a-3p, miR-942-5p, miR-149-5p, miR-32-5p, miR-144-3p, and miR-142-5p, were quantified in circulating exosomes from the control group ( n = 20 ) and the SCAD group ( n = 20 ) by quantitative real-time polymerase chain reaction (qPCR). Finally, the gene targets of the differentially expressed miRNAs were predicted, and the functions and signaling pathways of these targets were analyzed using an online database. The isolated exosomes had a bilayer membrane with a diameter of about 100 nm and expressed exosomal markers including CD63, Tsg101, and Flotillin but negatively expressed Calnexin. Both the exosome protein concentration and total protein amount exhibited no significant differences between the two groups. The qPCR assay demonstrated that among the eight miRNAs, the expression levels of miR-942-5p, miR-149-5p, and miR-32-5p in the serum exosomes from the SCAD group were significantly higher than that from the control group. And the three miRNAs for SCAD diagnosis exhibited AUC values of 0.693, 0.702, and 0.691, respectively. GO categories and signaling pathways analysis showed that some of the predictive targets of these miRNAs were involved in the pathophysiology processes of SCAD. In conclusion, our findings suggest that serum exosomal miR-942-5p, miR-149-5p, and miR-32-5p may serve as potential diagnostic biomarkers for SCAD.

The Embittered Mind

2016 ◽  
Vol 37 (4) ◽  
pp. 213-222 ◽  
Author(s):  
Hansjörg Znoj ◽  
Sandra Abegglen ◽  
Ulrike Buchkremer ◽  
Michael Linden
Keyword(s):  
Emotional Reaction ◽  
Control Group ◽  
Systematic Research ◽  
Roc Curve Analysis ◽  
Confirmatory Factor Analyses ◽  
Receiver Operating Characteristic Curves ◽  
Confirmatory Factor ◽  
Different Dimensions ◽  
First Time ◽  
Common Understanding

Abstract. There is a growing interest in embitterment as psychological concept. However, little systematic research has been conducted to characterize this emotional reaction. Still, there is an ongoing debate about the distinctiveness of embitterment and its dimensions. Additionally, a categorical and a dimensional perspective on embitterment have been developed independently over the last decade. The present study investigates the dimensions of embitterment by bringing these two different approaches together, for the first time. The Bern Embitterment Inventory (BEI) was given to 49 patients diagnosed with “Posttraumatic Embitterment Disorder (PTED)” and a matched control group of 49 patients with psychological disorders with other dominant emotional dysregulations. The ability to discriminate between the two groups was assessed by t-tests and Receiver Operating Characteristic Curves (ROC curve analysis). PTED patients scored significantly higher on the BEI than the patients of the control group. ROC analyses indicated diagnostic accuracy of the inventory. Further, we conducted Confirmatory Factor Analyses (CFA) to examine the different dimensions of embitterment and their relations. As a result, we found four characteristic dimensions of embitterment, namely disappointment, lack of acknowledge, pessimism, and misanthropy. In general, our findings showed a common understanding of embitterment as a unique but multidimensional emotional reaction to distressful life-events.

Cognitive dysfunctions associated with white matter damage due to cardiovascular burden – determinants and interpretations

2014 ◽  
Vol 45 (3) ◽  
pp. 334-345 ◽  
Author(s):  
Paweł Krukow
Keyword(s):  
Cerebral Cortex ◽  
White Matter ◽  
Cardiovascular Diseases ◽  
Cognitive Disorder ◽  
Theoretical Background ◽  
Dynamic Aspect ◽  
Pathological Changes ◽  
White Matter Damage ◽  
Neuropsychological Disorders ◽  
Considerable Research

AbstractAlthough considerable research has been devoted to cognitive functions deteriorating due to diseases of cardiovascular system, rather less attention has been paid to their theoretical background. Progressive vascular disorders as hypertension, atherosclerosis and carotid artery stenosis generate most of all pathological changes in the white matter, that cause specific cognitive disorder: disconnection syndromes, and disturbances in the dynamic aspect of information processing. These features made neuropsychological disorders secondary to cardiovascular diseases different than the effects of cerebral cortex damage, which may be interpreted modularly.

Expression Levels of MicroRNA-125b in Serum Exosomes of Patients with Asthma of Different Severity and its Diagnostic Significance

2019 ◽  
Vol 20 (10) ◽  
pp. 781-784 ◽  
Author(s):  
Meizhen Zhao ◽  
Li Juanjuan ◽  
Fan Weijia ◽  
Xie Jing ◽  
Huang Qiuhua ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Roc Curve ◽  
Quantitative Polymerase Chain Reaction ◽  
Persistent Asthma ◽  
Asthma Severity ◽  
Control Group ◽  
Spearman Correlation ◽  
Diagnostic Efficacy ◽  
Expression Levels ◽  
Serum Exosomes

Background: This study aimed to investigate the expression levels of microRNA (miRNA)-125b in serum exosomes and its diagnostic efficacy for asthma severity. Methods: The study included 80 patients with untreated asthma and 80 healthy volunteers. The patients were divided into 4 groups according to disease severity: 20 with the intermittent state, 20 with the mildly persistent state, 20 with the moderately persistent state, and 20 with the severely persistent state. The expression levels of miRNA-125b in serum exosomes of each group were detected using a quantitative polymerase chain reaction and compared. The Spearman correlation analysis was used to study the correlation between the expression levels of miRNA-125b in serum exosomes and asthma severity. The diagnostic efficacy of the expression levels of miRNA-125b in exosomes for asthma severity was evaluated using the Receiver Operating Characteristic (ROC) curve. Results: The expression levels of miRNA-125b in serum exosomes of patients with intermittent, mildly persistent, moderately persistent, and severely persistent asthma were all higher than those in the healthy control group, with statistically significant differences. The expression levels of miRNA-125b were also statistically significantly different among patients in each group. The Spearman correlation analysis showed a positive correlation of the relative expression of miRNA-125b in serum exosomes with asthma severity. The area under the ROC curve of the diagnostic efficacy of miRNA-125b in serum exosomes for patients with intermittent, mildly, moderately, and severely persistent asthma was 0.7770, 0.8573, 0.9111, and 0.9995, respectively. Conclusion: The expression levels of miRNA-125b in serum exosomes had a high diagnostic efficacy and might serve as a noninvasive diagnostic marker for asthma severity.

scholarly journals Diagnostic Application of Postmortem Cardiac Troponin I Pericardial Fluid/Serum Ratio in Sudden Cardiac Death

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 614
Author(s):  
Diana Hernández-Romero ◽  
María del Rocío Valverde-Vázquez ◽  
Juan Pedro Hernández del Rincón ◽  
José A. Noguera-Velasco ◽  
María D. Pérez-Cárceles ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Troponin ◽  
Cardiac Death ◽  
Troponin I ◽  
Sampling Site ◽  
Pericardial Fluid ◽  
Cardiac Troponin I ◽  
Control Group ◽  
Complementary Method

In approximately 5% of unexpected deaths, establishing a conclusive diagnosis exclusively on the basis of anatomo-pathological findings in a classic autopsy is difficult. Postmortem biomarkers have been actively investigated as complementary indicators to help to reach valid conclusions about the circumstances of death. Several studies propose either the pericardial fluid or peripheral veins as a location for troponin determination, but the optimum sampling site is still a matter of debate. Our objective was to evaluate the association between the ratio of troponin values in the pericardial fluid and serum (determined postmortem) and the diagnosis of acute myocardial infarction (AMI) in the context of sudden cardiac death. We included 175 forensic cases. Two groups were established: AMI deaths (48; 27.4%) and the control group (127; 72.6%). The cardiac Troponin I (cTnI) values in the pericardial fluid and the troponin ratio were found to be associated with the cause of death. Univariate regression analyses showed that both age and the cTnI ratio were significantly associated with the diagnosis of AMI death. In a multivariate analysis, adjusting for confounding factors, the age and cTnI ratio were independent predictors of death from myocardial infarction. We performed a receiver operating characteristic (ROC) curve for the cTnI ratio for AMI death and selected a cut-off point. Our biomarker was found to be a valuable and highly effective tool for use in the forensic field as a complementary method to facilitate diagnosis in nonconclusive autopsies.

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