Biomarker For Myocardial Infarction Research Articles

Trefoil factor-3 and galectin-4 as new candidates for prognostic biomarkers in ST-segment elevation myocardial infarction.

Trefoil factor-3 and galectin-4 as new candidates for prognostic biomarkers in ST-segment elevation myocardial infarction.

Angiopoietin-2 as a biomarker of non-ST-segment elevation myocardial infarction in patients with or without type 2 diabetes.

IntroductionAngiopoietin-2 (Ang-2) is a novel marker of coronary artery disease (CAD) and diabetes (DM). The aim was to evaluate Ang-2 as a potential new biomarker of non-ST elevation myocardial infarction (NSTEMI) in patients with or without type 2 DM (T2DM).Material and methodsThis was a multi-center, prospective study that included 138 (males: 91/66%) consecutive patients hospitalized due to NSTEMI, T2DM, or different cardiac disorders. The subjects were divided into four study groups: group A: 28 patients with NSTEMI and T2DM; group B: 47 patients with NSTEMI without T2DM; group C: 31 patients with T2DM, without a history of CAD; group D: 32 patients as a control group. Patients with NSTEMI underwent urgent coronarography. Clinical characteristics including biomarkers (hs-CRP, hsTnT, NT-proBNP, VEGF, HbA1c), SYNTAX SCORE, type of intervention (PCI vs. CABG), and number of implanted stents were taken into account in the analysis.ResultsSerum Ang-2 concentrations were significantly higher in patients with NSTEMI (group A: 1769 pg/ml; group B: 1757 pg/ml) and patients with T2DM (group C: 1993 pg/ml) as compared to the patients without CAD and without T2DM (group D: 866.8 pg/ml; p < 0.05). The prognostic accuracy of Ang-2 in NSTEMI diagnosis was determined with the area under the ROC curve (area under curve (AUC) = 0.63).ConclusionsAngiopoietin-2 serum concentration is elevated in the presence of NSTEMI in patients with and without T2DM and does not correspond to the degree of myocardial injury and hemodynamic status. Ang-2 remains elevated also in patients with T2DM without a history of CAD.

Systematically Analysis of lncRNA and microRNA Dynamic Features and Reveal Diagnostic and Prognostic Biomarkers in Myocardial Infarction

Background: The studies on long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) implicated in myocardial infarction (MI) have increased our understanding of gene regulatory mechanisms of MI. However, the dynamic features of lncRNAs and miRNAs in MI progression have not been investigated at a system level. Methods: Global lncRNA and miRNA expression and functional patterns were examined using time-series gene expression data. To identify early diagnostic and prognostic biomarkers of MI, an efficient computational method for identifying dysregulated lncRNA-miRNA-mRNA competing endogenous RNA triplets (LmiRM-CTs) was developed, and a support vector machine classification model was applied. Findings: We observed that the biggest response of cell stimulus on the transcriptome for mRNAs, lncRNAs and miRNAs all occurred in MI acute phase, and more protein-coding genes responded to cellular stimuli relative to non-coding RNAs. Biological functional analysis indicated that lncRNAs and miRNAs which were very sensitive to environmental changes and unstable during MI progression usually possessed less biological functions. We identified MI dynamic progression-related dysregulated LmiRM-CTs, from which a new panel of candidate diagnostic biomarkers defined by 7 lncRNAs were suggested to have high classification performance for patients with or without MI, and a new panel of prognostic biomarkers defined by 2 lncRNAs were identified with high discriminatory capability for MI patients who developed heart failure from those who did not. Interpretation: This study provides a foundation for understanding dynamic regulation features of lncRNAs and miRNAs during MI progression and facilitates the discovery of early diagnostic and prognostic biomarkers for MI. Funding Statement: This work was supported by the National Natural Science Foundation of China (Grant Nos. 31500675, 61602135), the Innovation Special Fund of Harbin Science and Technology Bureau of Heilongjiang Province (2017RAQXJ203), the Postdoctoral Foundation of Heilongjiang Province (LBH-Q17133) and the scientific research project of Heilongjiang Province Health and Family Planning Commission (Grant Nos. 2016-131). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Not required.

Chemiluminescence Immunoassays for Simultaneous Detection of Three Heart Disease Biomarkers Using Magnetic Carbon Composites and Three-Dimensional Microfluidic Paper-Based Device

Chemiluminescence (CL) immunoassays for simultaneous detection of early acute myocardial infarction (AMI) biomarkers, including copeptin, heart-type fatty acid binding protein (h-FABP), and cardiac troponin I (cTnI), were developed by using Co2+/N-(aminobutyl)-N-(ethylisoluminol) (ABEI) functionalized magnetic carbon composite (Co2+-ABEI-Fe3O4@void@C) as an interface and a three-dimensional microfluidic paper-based device (3D μPAD) as a detection system. For CL immunoassays, Co2+-ABEI-Fe3O4@void@C was assembled with chitosan (CS) and gold nanoparticle-conjugated antibody (Au-Ab) sequentially to form the sensing platform (Co2+-ABEI-Fe3O4@void@C-CS/Au-Ab). In the presence of antigen (Ag), Ag was captured by the sensing interface to form an immunocomplex, leading to an increase in CL intensity due to the catalysis of -COO- existing in Ag. A 3D μPAD with three detection zones for simultaneous detection of copeptin, h-FABP, and cTnI was designed and fabricated to obtain time-resolved CL signals. Three kinds of immunocomplexes formed with copeptin, h-FABP, and cTnI were added to three detection zones of 3D μPAD, respectively. After injecting H2O2, three time-resolved CL signals were generated in one CL detection run by virtue of time-delayed transport of H2O2 to different detection zones. The three time-resolved CL signals were used for the simultaneous determination of copeptin, h-FABP, and cTnI. The detection limit of copeptin, h-FABP, and cTnI was 0.40 pg/mL, 0.32 pg/mL, and 0.50 pg/mL, respectively, which is at least 1 order of magnitude lower than most of the reported immunoassays. The immunoassays could be directly used for the detection of copeptin, h-FABP, and cTnI in human serum samples. The proposed immunoassays are simple, fast, sensitive, and selective, and are of great application potential in early diagnosis and treatment of AMI.

Multiplexed chemiluminescence determination of three acute myocardial infarction biomarkers based on microfluidic paper-based immunodevice dual amplified by multifunctionalized gold nanoparticles

Acute myocardial infarction (AMI) causes significant mortality and morbidity. The determination of multiple AMI biomarkers is very important for the timely diagnosis of AMI. In this work, simultaneous determination of three AMI biomarkers were achieved by virtue of a three-dimensional (3D) microfluidic paper-analytical device (μPAD) with temporally resolved chemiluminescence (CL) emissions for the first time. A dual-signal amplification strategy was introduced including by employing primary antibody functionalized gold nanoparticles (Ab1-GNPs) immobilized on the detection zone as amplified capture probes, and Co(II) catalyst, secondary antibody, luminol multifunctionalized gold nanoparticles (Co(II)-Ab2-luminol-GNPs) with excellent CL activity as amplified signal probes. CL immunoreactions were performed at three detection zone of the fabricated 3D μPAD by assembling Ab1-GNPs, antigen, and Co(II)-Ab2-luminol-GNPs to form sandwich-type immunocomplexes. Auto separated CL signals with temporal resolution were obtained by time delayed transport of H2O2 to different detection zones for multiplexed analysis. The CL signal obtained by using Co(II)-Ab2-luminol-GNPs as signal probe (10576 a.u.) were about 20-fold higher than that by using conventional horseradish peroxidase labeled antibody modified luminol-GNPs as signal probe (531 a.u.). Finally, three AMI biomarkers including heart-type fatty acid-binding protein (H-FABP), cardiac troponin I (cTnI) and copeptin were quantitatively analyzed in one CL detection run by reading the CL intensity of the obtained three CL emission peaks. The detection range were ultra-wide ranged from 0.1 pg/mL to 1 μg/mL, 0.5 pg/mL to 1 μg/mL and 1 pg/mL to 1 mg/mL with the detection limits down to 0.06 pg/mL, 0.3 pg/mL and 0.4 pg/mL for H-FABP, cTnI and copeptin detection, respectively. The developed μPAD based immunoassay performing multiplexed analysis ability, high sensitivity, ultra-wide dynamic range, favorable selectivity, accessible accuracy and reproducibility, have great application potential for the early diagnosis of AMI.

An electrochemical troponin I peptisensor using a triangular icicle-like gold nanostructure

Detection of troponin I (TnI), as a unique biomarker for myocardial infarction (MI), is highly important for diagnosis, prevention and therapy of MI, a major problem in the health policy and death. A triangular icicle-like gold nanostructure was firstly electrodeposited on a gold substrate to attain a high-surface area transducer, and characterized by field emission scanning electron microscopy. A 13-amino acid affinity peptide was then immobilized on the gold nanostructure surface to fabricate a TnI peptide-based biosensor, namely as peptisensor. The K3Fe(CN)6/K4Fe(CN)6 couple was applied as a redox marker to detect and quantify the TnI binding into the peptisensor surface. The times of peptide immobilization on the gold nanostructure and binding with TnI were optimized. Using the redox marker of ferro/ferricyanide and differential pulse voltammetry, we quantified TnI in a concentration range of 0.01–5 ng mL−1 with a detection limit of 0.9 pg mL−1. The fabrication reproducibility, stability over time and endurance of interfering effect of the peptisensor were evaluated. The peptisensor was finally applied for analysis of human serum samples.

Circulating microRNAs as predictive biomarkers of myocardial infarction: Evidence from the HUNT study

Background and aimsSeveral risk prediction models for coronary heart disease (CHD) are available today, however, they only explain a modest proportion of the incidence. Circulating microRNAs (miRs) have recently been associated with processes in CHD development, and may therefore represent new potential risk markers. The aim of the study was to assess the incremental value of adding circulating miRs to the Framingham Risk Score (FRS). MethodsThis is a case-control study with a 10-year observation period, with fatal and non-fatal myocardial infarction (MI) as endpoint. At baseline, ten candidate miRs were quantified by real-time polymerase chain reaction in serum samples from 195 healthy participants (60–79 years old). During the follow-up, 96 participants experienced either a fatal (n = 36) or a non-fatal MI (n = 60), whereas the controls (n = 99) remained healthy. By using best subset logistic regression, we identified the miRs that together with the FRS for hard CHD best predicted future MI. The model evaluation was performed by 10-fold cross-validation reporting area under curve (AUC) from the receiver operating characteristic curve (ROC). ResultsThe best miR-based logistic regression risk-prediction model for MI consisted of a combination of miR-21-5p, miR-26a-5p, mir-29c-3p, miR-144-3p and miR-151a-5p. By adding these 5 miRs to the FRS, AUC increased from 0.66 to 0.80. In comparison, adding other important CHD risk factors (waist-hip ratio, triglycerides, glucose, creatinine) to the FRS only increased AUC from 0.66 to 0.68. ConclusionsCirculating levels of miRs can add value on top of traditional risk markers in predicting future MI in healthy individuals.

Identification of key genes involved in myocardial infarction

BackgroundThis study focuses on the identification of conserved genes involved in myocardial infarction (MI), and then analyzed the differentially expressed genes (DEGs) between the incident and recurrent events to identify MI-recurrent biomarkers.MethodsGene expression data of MI peripheral blood were downloaded from GSE97320 and GSE66360 datasets. We identified the common DEGs in these two datasets by functional enrichment analysis and protein–protein interaction (PPI) network analysis. GSE48060 was further analyzed to validate the conserved genes in MI and to compare the DEGs between the incident and recurrent MI.ResultsA total of 477 conserved genes were identified in the comparison between MI and control. Protein–protein interaction (PPI) network showed hub genes, such as MAPK14, STAT3, and MAPKAPK2. Part of those conserved genes was validated in the analysis of GSE48060. The DEGs in the incident and recurrent MI showed significant differences, including RNASE2 and A2M-AS1 as the potential biomarkers of MI recurrence.ConclusionsThe conserved genes in the pathogenesis of MI were identified, benefit for target therapy. Meanwhile, some specific genes may be used as markers for the prediction of recurrent MI.

Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone

Extracellular vesicles (EVs) are submicron, membrane-enclosed particles that are released from cells in various pathophysiological states. The molecular cargo of these vesicles is considered to reflect the composition of the cell of origin, and the EV proteome is therefore a potential source of biomarkers for various diseases. Our aim was to determine whether EVs isolated from plasma provide additional diagnostic value or improved pathophysiological understanding compared to plasma alone in the context of myocardial infarction (MI). A panel of proximity extension assays (n = 92) was employed to analyze EV lysates and plasma from patients with MI (n = 60) and healthy controls (n = 22). After adjustment for multiple comparisons, a total of 11 dysregulated proteins were identified in EVs of MI patients compared to the controls (q < 0.01). Three of these proteins: chymotrypsin C (CTRC), proto-oncogene tyrosine-protein kinase SRC (SRC) and C-C motif chemokine ligand 17 (CCL17) were unaltered in the corresponding plasma samples. As biomarkers for MI, rudimentary to no evidence exists for these proteins. In a separate group of patients with varying degrees of coronary artery disease, the decrease in EV-associated (but not plasma-related) SRC levels was confirmed by ELISA. Confirmation of the presence of SRC on EVs of different sizes and cellular origins was performed with ELISA, flow cytometry and nanoparticle tracking analysis. In conclusion, the data revealed that despite a similarity in the EV and plasma proteomes, analysis of isolated EVs does indeed provide additional diagnostic information that cannot be obtained from plasma alone.

EGF-like repeats and discoidin I-like domain 3 (EDIL3) deficiency improves post-myocardial infarction healing via neutrophil extracellular traps (NETs) mediated pro-inflammatory macrophage polarization

Abstract After myocardial infarction (MI), injured cardiomyocytes recruit neutrophils, leading to extravasated monocytes polarized to inflammatory and reparative macrophages sequentially, which contribute to the healing and regenerative process. As an endogenous leukocyte-endothelial adhesion inhibitor, the role of EDIL3 in MI remains obscure. We found that serum EDIL3 level of MI patients was negatively associated with MI biomarkers, including CK-MB, cTnI and MGB. EDIL3−/− mice showed improved infarct healing with lower mortality, better cardiac function and decreased infarcted size compared with wild type (WT). Enhanced neutrophil infiltration resulted in the increase of Ly6Chi MHClo Mertk− macrophages, which we identified to be pro-inflammatory, protecting EDIL3−/− mice hearts from excessive fibrosis. A neutrophil infiltration antagonist not only eliminated the difference in cardiac function between WT and EDIL3−/− mice, but also reduced Ly6Chi MHClo Mertk− macrophage polarization. These data implied that improved cardiac healing was associated with increased infiltration of neutrophil and it mediated macrophage polarization. Notably, we confirmed that this polarization depended on NETs, which were more abundant in hearts and serum in EDIL3−/− mice than in WT. Indeed, self-DNA released from NETs primed the pro-inflammatory polarization of macrophages. The degradation of NETs by DNase I reduced this polarization and thus affected post-MI outcome, indicating the pivotal role of NETs in MI healing. Meanwhile, the pro-inflammatory macrophages induced apoptosis of neutrophils and restrained excessive inflammation. Our findings reveal a novel neutrophil–macrophage crosstalk essential to cardiac healing after MI.

Ratiometric fluorescent immunoassay for the cardiac troponin-I using carbon dots and palladium-iridium nanocubes with peroxidase-mimicking activity.

A nanozyme-linked immunosorbent assay is described for cardiac troponin I which is a biomarker for myocardial infarction. The method is based on the use of Pd-Ir nanocubes with excellent peroxidase-like activity. The nanocubes catalyze the oxidization of nonfluorescent o-phenylenediamine (OPD) by H2O2 to form a yellow fluorescent product (oxOPD) with excitation/emission maxima at 400/570nm. Carbon dots are added as areference fluorophore. Under the same excitation wavelength, they display blue fluorescence (450nm). The ELISA uses the Pd-Ir nanocubes as a label for the secondary antibody and OPD as substrate. The ratio of fluorescence intensities at 570 and 450nm increases in the 1pg·mL-1 to 1ng·mL-1 cardiac troponin I concentration range, and the detection limit is 0.31pg·mL-1. The method was applied to analyze spiked serum samples, and the results compared well with those obtained by a commercial chemiluminescence assay. Graphical abstract Schematic presentation of the ratiometric fluorescence immunoassayforcardiac troponin-I.Pd-Ir nanocubes were employed to fabricate nanozyme-based signal labels for its excellent peroxidase-mimicking activity.

Study of Stability and Sensitivity of Cardiac Troponin I Based on FET Sensor

One of the most important protein biomarkers for myocardial infarction in the blood is cardiac troponin I (cTnI). However, in order to develop a cTnI FET sensor that allows patients to regularly track cardiovascular diseases (CVDs), the sensor must perform better sensitivity, stability and reproducibility.In this study, in order to find out the mechanism which can raise the stability and sensitivity of cTnI FET sensor without changing the chip design, there are two methods was utilized — different gate voltages (Vg) of MOSFET and different anti-cTnI concentrations. The results of this study can be used as a significant basis for optimizing hand-held cTnI biosensor in the future.

Differential urinary proteomics analysis of myocardial infarction using iTRAQ quantification.

Myocardial infarction (MI) is a disease characterized by high morbidity and mortality rates. MI biomarkers are frequently used in clinical diagnosis; however, their specificity and sensitivity remain unsatisfactory. Urinary proteome is an easy, efficient and noninvasive source to examine biomarkers associated with various diseases. The present study, to the best of the authors' knowledge, is the first to examine the urinary proteome using the isobaric tags for relative and absolute quantitation (iTRAQ) technology to identify potential diagnostic biomarkers of MI. The urinary proteome was analyzed within 12 h following the first symptoms of early-onset MI and at day 7 following percutaneous coronary intervention via iTRAQ labeling and two-dimensional liquid chromatography-tandem mass spectrometry. Candidate biomarkers were validated by multiple reaction monitoring (MRM) analysis. A total of 233 urinary proteins were differentially expressed. Gene enrichment analysis identified that the urinary proteome in patients with MI was associated with atherosclerosis, abnormal coagulation and abnormal cell metabolism. In total, 12 differentially expressed urinary proteins were validated by MRM analysis, five of which were associated with MI for the first time in the present study. Binary logistic regression analysis suggested that the combination of five urinary proteins (antithrombin-III, complement C3, α-1-acid glycoprotein 1, serotransferrin and cathepsin Z) may be used to diagnose MI with 94% sensitivity and 93% specificity. In addition, the protein expression levels of three proteins were significantly restored to normal levels following surgical treatment. The verified candidate biomarkers may be used for the diagnosis of MI, and for monitoring the disease status and the effects of treatments for MI. The present results may facilitate future clinical applications of the urinary proteome to diagnose MI.

An aptasensor for troponin I based on the aggregation-induced electrochemiluminescence of nanoparticles prepared from a cyclometallated iridium(III) complex and poly(4-vinylpyridine-co-styrene) deposited on nitrogen-doped graphene.

An ultrasensitive electrochemiluminescence (ECL) disposable aptamer sensor (aptasensor) is presented for detection of myocardial infarction biomarker by quantification of troponin I in blood serum. A screen-printed electrode was modified with (a) aptamer-modified gold nanoparticles, (b) cyclometallated iridium(III)-poly-4-vinylpyridine nanoparticles, and (c) nitrogen-doped graphene in order to increase the loading capacity and conductivity of the aptasensor. If the aptasensor is exposed to troponin I, it will bind to the aptamer and desorb the aptamer from gold nanoparticles and the surface of the electrode. This generates an enhancement in ECL emission depending on troponin I concentration. ECL emission is strongly improved by aggregation-induced phenomenon, which is caused by inhibition of the water and oxygen quenching effect on the iridium complex ECL in aqueous media. Under optimum conditions, the aptasensor has a wide dynamic range that extends from 0.1 pM to 10nM, with a 20 fM detection limit (S/N = 3) and a relative standard deviation of 3.1%. The ECL aptasensor was successfully applied to 20 individual human serum for the detection of troponin I biomarker. Graphical abstract Schematic presentation of electrochemiluminescence aptamer assay fabrication for detection of Troponin I. Carbon screen printed electrode (CSPE) was modified with nitrogen doped graphene (NG), gold nanoparticles (AuNPs), cyclometallated iridium(III)-polyvinylpyridine polymer nanoparticles, ionic liquid and bovine serum albumin.

The whole transcriptome and proteome changes in the early stage of myocardial infarction

As the most severe manifestation of coronary artery disease, myocardial infarction (MI) is a complex and multifactorial pathophysiologic process. However, the pathogenesis that underlies MI remains unclear. Here, we generated a MI mouse model by ligation of the proximal left anterior descending coronary artery. The transcriptome and proteome, at different time points after MI, were detected and analysed. Immune-related pathways, cell cycle-related pathways, and extracellular matrix remodelling-related pathways were significantly increased after MI. Not only innate immune cells but also adaptive immune cells participated in the early stage of MI. Proteins that functioned in blood agglutination, fibrinolysis, secretion, and immunity were significantly changed after MI. Nppa, Serpina3n, and Anxa1, three secreted proteins that can easily be detected in blood, were significantly changed after MI. Our discoveries not only reveal the molecular and cellular changes in MI but also identify potential candidate biomarkers of MI for clinical diagnosis or treatment.

Identification of lncRNA competitively regulated subpathways in myocardial infarction.

The functions of long non-coding RNAs (lncRNAs) in myocardial infarction (MI) remain largely unknown. Thus, we used the subp athway-LINCE method to characterize the potential roles of lncRNAs in MI. Candidate lncRNA-mRNA interactions were obtained from miRNA-mRNA interactions and lncRNA-miRNA interactions. Then the lncRNA and mRNA co-expression relationship pairs (LncGenePairs) were screened from the lncRNAs and mRNA intersections, which were extracted through candidate lncRNA-mRNA interactions and sample gene expression profiles. The lncRNAs in LncGenePairs were embedded into pathway graphs as nodes through linking to their regulated mRNAs, which resulted in obtaining condition-specific lncRNA competitively regulated signal pathways (csLncRPs). Finally, the csLncRPs were calculated using lenient distance similarity to obtain the lncRNA competitively regulated subpathways. Based on the statistical significance of signal subpathways, lncRNA-mRNA networks were constructed, in which hub lncRNAs were selected. A total of 65 lncRNAs competitively regulated subpathways and 13 hub lncRNAs were obtained, which associated with a risk of MI. Identifying lncRNAs competitively regulated subpathways not only provides potential lncRNA biomarkers for MI, but also helps the understanding of pathogenesis of MI.

STUDY OF PANEL OF DIAGNOSTIC CARDIAC MARKERS FOR ACUTE MYOCARDIAL INFARCTION

Objectives: The aim of this study is to estimate the level of creatine kinase-myocardial band (CK-MB), C-reactive protein (CRP), and lactate dehydrogenase (LDH) biomarker in myocardial infarction (MI) (troponin T-positive) and compare with normal healthy individuals (Troponin-T [TnT] negative).&#x0D; Methods: A cross-sectional study on 172 patients involving 100 patients with nondiabetic MI and 72 apparently healthy controls with no history of diabetes and/or MI was done from December 2017 to May 2018. The diagnosis of MI was established with electrocardiogram findings and TnT estimation. Blood samples were gathered and processed for the estimation of CK-MB, LDH, and CRP.&#x0D; Results: The mean age of the cases was 62.15±7.75 years and in the controls was 61.49±8.35 years (p=0.592). The mean value of CK-MB, LDH, and CRP in the TnT positive group was 111.94±29.59 IU/L, 564.43±110.99 IU/L, and 15.69±4.04 mg/L, whereas in the TnT negative group was 16.36±3.77 IU/L, 223.68±36.23 IU/L, and 6.08±2.02 mg/L, respectively (p&lt;0.0001). CK-MB was deranged in 100% of TnT positive group, and in only 2.78% in TnT negative group (p&lt;0.0001). LDH was deranged in 100% TnT positive group, and in 16.67% in TnT negative group (p&lt;0.0001). CRP was deranged in 4% TnT positive group, and in 0% in TnT negative group (p=0.141).&#x0D; Conclusion: This study indicated that CK-MB and LDH are sensitive cardiac markers for the diagnosis of MI.

Simultaneous colorimetric determination of acute myocardial infarction biomarkers by integrating self-assembled 3D gold nanovesicles into a multiple immunosorbent assay.

An improved enzyme-free immunosorbent assay is described for the simultaneous detection of the myocardial infarction biomarkers N-terminal pro B type natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), and cardiac muscle troponin T (cTnT). The assay integrates 3D gold nanovesicles (GNVs) and three allochroic agents (phenolphthalein,methyl red,bromothymol blue). The pH regulated allochroic agents were enwrapped in GNVs to acts as ultrasensitive nanoprobes. Loading can be controlled by adjusting the temperature to efficiently load and release the allochroic agents. This bare-eye multicolor assay has limits of detection of 70pg·mL-1 for NT-proBNP, 910pg·mL-1 for CK-MB, and 7.8pg·mL-1 for cTnT. Other features include (a) a linear range that extends over a wide range and sometimes is better than conventional HRP-based immunoassays, and (b) a precision that is comparable to immunofluorescence assays as used in the clinical laboratory. Graphical abstract Schematic presentation of an improved enzyme-free immunosorbent assay (EFISA). It integrates 3D gold nano-vesicles (GNVs) and allochroic agents for the simultaneous detection of acute myocardial infarction (AMI) biomarkers (N-terminal prohormone of brain natriuretic peptide (NT-proBNP), kinase-muscle/brain test (CK-MB), and cardiac muscle troponin (cTnT)).

Role of high-sensitivity troponin T as a sensitive biomarker for postoperative myocardial infarction and outcome after isolated coronary artery bypass grafting surgery

Background Uncertainty exists about the diagnosis of post-coronary artery bypass grafting (CABG) Perioperative myocardial infarction (PMI) owing to nonconsensus for elevated biomarkers diagnostic levels and associated criteria. Post-CABG studies concerning high-sensitivity troponin (hs-TnT) and its role in the diagnosis of postoperative MI are few. Aim We are aiming to figure out the diagnostic and prognostic role of hs-TnT in individuals undergoing isolated coronary artery bypass graft surgery and whether it has relations to other diagnostic criteria. Patients and methods A total of 50 patients with multivessel coronary artery disease who elected for isolated CABG were enrolled in the study. Our exclusion criteria included individuals with chronic renal impairment, sepsis, and pre-existing high level of hs-TnT (unless >50% increment significantly raises its postoperative difference). Moreover, patients who experienced marked intraoperative hypotension (mean arterial blood pressure 5 min) were excluded. Levels of 140 ng/l (10 times 99th percentile upper reference limit) and 500 ng/l (10 times coefficient of variation of 10% for fourth-generation troponin T applied to hs-TnT) were predetermined. Results We enrolled 50 patients who underwent elective CABG. Their mean age was 59.8 ± 6.5 years, and there were 30 (60%) males. hs-TnT level was significantly associated with a higher incidence of off-pump CABG, higher cardiopulmonary bypass time, and higher aortic cross-clamp time. The composite morbidity was significantly higher in patients with hs-TnT level more than 500 (P Conclusion The occurrence of post-CABG MI is associated with a higher level of hs-TnT as well as a higher incidence of morbidity and mortality. The use of hs-TnT to diagnose post-CABG MI with a cut point of 10 times 99th percentile upper reference limit especially if associated with ECG and/or echocardiographic criteria predicts 30-day mortality.

Smartphone-app based point-of-care testing for myocardial infarction biomarker cTnI using an autonomous capillary microfluidic chip with self-aligned on-chip focusing (SOF) lenses.

Cardiovascular disease is one of the most common causes of mortality in the world. Most of the diagnostic processes usually require bulky instruments and trained professionals, which cannot meet the demand for fast, early and regular bedside diagnosis. In this paper, a bespoke app on a smartphone and an autonomous capillary microfluidic chip (ACMC) are combined to realize the point-of-care testing of cardiac troponin I (cTnI). The smartphone-app-ACMC platform was based on the sandwich immunofluorescence principle and featured self-aligned on-chip focusing (SOF) lenses which can avoid the complex optical coupling process. The operator only needs to introduce 100 μl sample into the ACMC, where the priming, time-delaying, mixing and washing steps for the assay can be accomplished automatically. With the help of the bespoke app and a palm-sized optical attachment, the smartphone can capture fluorescence images, process fluorescence intensity information, output detection results and save the results for long-term monitoring. Our results showed that within 12 min, the detection limit of 78 pg ml-1 and 94 pg ml-1 for cTnI was attained in buffer and spiked human serum, respectively. Our proposed platform has the potential to be applied in the POCT field especially for some resource-limited settings.