Biomarkers For Acute Myocardial Infarction Research Articles

Rapid diagnosis of acute myocardial infarction based on reverse transcription-accelerated strand exchange amplification of miR-208a.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease associated with high morbidity and mortality, posing a significant threat to human health. Therefore, early diagnosis of AMI has become a focal point of research. MiR-208 is specifically expressed in the heart and is involved in the regulation of cardiomyocyte hypertrophy, cardiac fibrosis, and other myocardial gene expressions. It is expected to be applied in the clinical detection of AMI due to its release by damaged myocardial cells within 3 hours of AMI. In this study, we developed a denatured bubble-mediated reverse transcription-accelerated strand exchange amplification (RT-ASEA) method to detect the early biomarker miR-208a of AMI. The novel approach allowed rapid amplification of miR-208a in 15 minutes, with good performance in terms of repeatability (CV < 6%), determination limit (1 × 100 pmol L-1), and linearity (R2 = 0.9690). Based on the analysis of 42 clinical samples, a strong correlation was observed between the Ct value of miR-208a detected by the RT-ASEA method and the cTnI concentration, considered the gold standard for diagnosis of AMI. The research suggested that the RT-ASEA method could be applied to distinguish between AMI and healthy groups. The area under the receiver operating characteristic curve (AUC) was 0.9976, with a sensitivity of 96% and a specificity of 100%. Optimized RT-ASEA is a reliable and efficient method for miRNA detection. Furthermore, this study provides crucial data support for the development of miR-208a as an early biomarker for AMI, which is of great significance in life and health.

A carbon quantum layer modified BiVO4 photoelectrochemical aptamer biosensor for ultra-sensitive cTnI biomarker detection based on the interface nephelauxetic effect and heterojunction assistance.

The sensitivity and specificity of a semiconductor photoelectrochemical (PEC) aptamer biosensor are determined by the separation and transport of the photoinduced carriers as well as aptamer probe immobilization. In this study, an in situ thermal transformation organic polymer strategy was employed to produce an ∼2.5 nm carbon quantum layer on the surface of the BiVO4(BVO) photoanode. Experimental tests and theoretical calculations have revealed that this carbon quantum layer-coated BVO(C@BVO) heterostructure could generate surface charge depletion regions through an interface nephelauxetic effect. These charge depletion regions facilitated the efficient immobilization of DNA aptamer probes of the acute myocardial infarction biomarker cardiac troponin I (cTnI), while showing almost no immobilization capability on a pure-phase C quantum layer or BVO crystals. Simultaneously, the formation of the C@BVO heterostructure also enhanced the directional transport of photo-generated holes from BVO to the C quantum layer. Due to the above reasons, the C@BVO PEC aptamer biosensor achieved a linear detection range for cTnI from 10-14 g L-1 to 10-10 g L-1, with a record detection limit (LOD) of ∼0.33 × 10-14 g L-1 (N > 3). Meanwhile, the biosensor also demonstrated well the detection reproducibility and specificity for cTnI detection. Therefore, the strategy of using a carbon quantum layer-coated PEC electrode shows good potential to develop PEC biosensors with high sensitivity, specificity, and robustness.

43 CARDIAC TROPONINS AND COVID-19: WHAT DO WE KNOW ABOUT HETEROPHILIC ANTIBODIES?

Abstract Background During the Coronavirus disease-19 (COVID-19) pandemic, a significant increase in cardiovascular events and death for acute Myocardial Infarction (AMI) has been widely described. In turn, cardiac troponins represent the main serum diagnostic biomarkers of AMI. However, several mechanisms of troponins elevation other than AMI could be identified such as the analytic interference due to the Heterophilic Antibodies (HA), which represents a less explored and underestimated cause. Methods The research of the following keywords “Heterophilic” or “Heterophile Antibodies” associated with “Troponin”, “Troponin I”, “Troponin T” or “High-sensitive Troponin” have identified 73 works in the most popular bibliographic databases such as PubMed, Scopus, and Web of Science, in which the first was published in 1998. In our systematic review, the inclusion criteria have considered all the works in which clinical information about the patients are described. The results have included 55 papers for an overall population of 128 cases that have presented HA's interference in troponins’ assay. In the great part of the works, HA's capture test has been performed to diagnose this interference. The association between HA and COVID-19 has also been explored with the identification of three works in scientific literature. In addition, we reported a clinical case of a young patient with persistent high serum ultra-sensitive Troponin levels due to HA, during the COVID-19 pandemic. Results The results have indicated the most at-risk population in patients with a history of multiple hospitalizations and with poor cardiovascular risk factors, who usually complained of atypical chest pain combined with persistent elevation of cardiac troponins without high CK-MB values. Instead, only a few data could be isolated in the literature about HA's interference on troponins essay in COVID-19 patients. However, has been widely ascertained how increased serum levels of cardiac troponins have been identified in most of the SARS-COV-2 swabs positive populations, and several cardiac and extracardiac mechanisms may explain this condition. Conclusions The description of the most common clinical features of patients with HA's interference could help clinicians to early recognize this phenomenon, reducing the number of instrumental examinations and the hospitalization period of these patients. Therefore, the analytical mistake due to HA could be always considered in AMI differential diagnosis, and the use of HA's capture test in the at-risk population may determine an early diagnosis. Finally, the HA's phenomenon could increase during the COVID-19 period, considering how infections and vaccinations may stimulate heterophile's activity.

Cardiac troponins: Mechanisms of release and role in healthy and diseased subjects.

The cardiac troponins (cTns), cardiac troponin C (cTnC), cTnT, and cTnI are key elements of myocardial apparatus, fixed as protein complex on the thin filament of sarcomere and are involved in the regulation of excitation-contraction coupling of cardiomyocytes in the presence of Ca2+ . Circulating cTnT and cTnI (cTns) increase following cardiac tissue necrosis, and they are consolidated biomarkers of acute myocardial infarction (AMI). However, the use of high sensitivity (hs)-immunoassay tests for cTnT and cTnI has made it possible to identify a multitude of other clinical conditions associated with increased circulating levels of cTns. cTns can be measured also in the peripheral circulation of healthy subjects or athletes, suggesting that different mechanisms are involved in the release of cTns in the blood independently of cardiac cell necrosis. In this review, the molecular/cellular mechanisms involved in cTns release in blood and the exploitation of cTnI and cTnT as biomarkers of cardiac adverse events, in addition to cardiac necrosis, are discussed.

Triple Enhancement for Sensitive Immunochromatographic Assay: A Case Study for Human Fatty Acid-Binding Protein Detection.

The work considers a combination of three enhancing approaches for immunochromatographic assay (ICA) and the integration of their impacts into changes of the limit of detection (LOD). Human fatty acid binding protein (FABP), an early biomarker of acute myocardial infarction, was the target analyte. Starting from the common ICA protocol with an LOD equal to 11.2 ng/mL, three approaches were realized: (1) replacement of spherical gold nanoparticles with gold nanoflowers having a branched surface (20-fold lowering the LOD); (2) enhanced labeling of immune complexes via nanoparticle aggregates (15-fold lowering); (3) in-situ growth of bound nanoparticles by reduction of gold salts (3-fold lowering). Single and combined implementations of these approaches have been studied. It has been shown that the LOD decrease for combined approaches is close to the multiplied contribution of each of them. The final LOD for FABP was 0.05 ng/mL, which is 220 times lower than the LOD for the common ICA protocol. The efficiency of the enhanced ICA with three combined approaches was confirmed by testing human serum samples for FABP presence and content. The development presents a new efficient technique for rapid sensitive detection of FABP for medical diagnostics. Moreover, the demonstrated multiple enhancements could be applied for various demanded analytes.

Transcriptomic Profiling Unravels Novel Deregulated Gene Signatures Associated with Acute Myocardial Infarction: A Bioinformatics Approach

Acute myocardial infarction (AMI) is a severe disease with elevated morbidity and mortality rate worldwide. This is attributed to great losses of cardiomyocytes, which can trigger the alteration of gene expression patterns. Although several attempts have been made to assess the AMI biomarkers, to date their role in rescuing myocardial injury remains unclear. Therefore, the current study investigated three independent microarray-based gene expression datasets from AMI patients (n = 85) and their age-sex-matched healthy controls (n = 70), to identify novel gene signatures that might be involved in cardioprotection. The differentially expressed genes (DEGs) were analyzed using 'GEO2R', and weighted gene correlation network analysis (WGCNA) was performed to identify biomarkers/modules. We found 91 DEGs, of which the number of upregulated and downregulated genes were 22 and 5, respectively. Specifically, we found that the deregulated genes such as ADOR-A3, BMP6, VPS8, and GPx3, may be associated with AMI. WGCNA revealed four highly preserved modules among all datasets. The 'Enrichr' unveiled the presence of miR-660 and STAT1, which is known to affect AMI severity. Conclusively, these genes and miRNA might play a crucial role the rescue of cardiomyocytes from severe damage, which could be helpful in developing appropriate therapeutic strategies for the management of AMI.

Traditional and novel diagnostic biomarkers for acute myocardial infarction

Abstract Background Acute myocardial infarction (AMI) is a leading cause of death worldwide. The first hours of acute myocardial infarction are correlated with the highest risk of death. Therefore, early diagnosis of the infarction seriously affects the efficacy of the treatment administered to the patient. Misdiagnosing patients with chest pain often leads to inappropriate admission of them as acute myocardial infarction patients. The physical examination of the patient, the electrocardiogram, and the assessment of cardiac biomarkers all play an important role in the early diagnosis of acute ischemia, along with the patient's medical history. Main body The present review highlights a number of different biomarkers that are released and elevated in blood during an acute myocardial infarction. Conclusions Analysis of cardiac biomarkers has become the first-line diagnostic tool used in the diagnosis of acute myocardial infarction. Novel markers of acute myocardial infarction, when added to routinely used markers, can provide added value not only in the earlier detection of acute myocardial infarction but also in monitoring the clinical progress of the disease, predicting its consequences, evaluating its prognosis, detecting recurrence, and managing its treatment. This leads to a lower mortality rate associated with acute myocardial infarction. cMyC, IMA, S100, and MicroRNAs can serve as markers of early diagnosis of acute myocardial infarction, whereas myeloperoxidase, sCD40L, PAPPA, and TNF-α can be used to monitor the clinical progress of the disease. In addition, H-FABP, GDF-15, F2 isoprostanes, and ST2 can serve as predictors of AMI complications and mortality. Copeptin, ST2, and SIRT can be useful as prognostic markers of acute myocardial infarction.

Reporter Molecules Embedded Au@Ag Core-Shell Nanospheres as SERS Nanotags for Cardiac Troponin I Detection

Rapid and accurate detection of acute myocardial infarction can improve patients' chances of survival. Cardiac troponin I (cTn I) is an important diagnostic biomarker for acute myocardial infarction. However, current immunoassays are insufficient to accurately measure cTn I, as they have limited detection sensitivity and are time-consuming. Surface-enhanced Raman scattering (SERS) is a brilliant fingerprints diagnostic technique characterised by ultrasensitivity, fast response, and qualitative and quantitative analysis capabilities. In this study, reporter molecules (4-Mercaptobenzoic acid, 4-MBA) embedded Au@Ag core-shell nanospheres as SERS nanotags were prepared for the detection of cTn I. As the Raman reporters were embedded between the core and the shell, they could be protected from the external environment and nanoparticle aggregation. Excellent SERS performances were obtained due to the enhanced local electromagnetic field in the gap of core and shell metals. In a standard phosphate buffered saline (PBS) environment, the limit of detection for cTn I was 0.0086 ng mL-1 (8.6 ppt) with a good linear relationship. The excellent Raman detection performance was attributed to the localized surface plasmon resonance effect and strong electromagnetic field enhancement effect produced by the gap between the Au core and the Ag shell. The SERS nanotags we prepared were facile to synthesize, and the analysis procedure could be completed quickly (15 min), which made the detection of cTn I faster. Therefore, the proposed SERS nanotags have significant potential to be a faster and more accurate tool for acute myocardial infarction diagnostics.

Rapid simultaneous SERS detection of dual myocardial biomarkers on single-track finger-pump microfluidic chip

Acute myocardial infarction (AMI) is a serious disease with high mortality that afflicts many people around the world. The main cause of death from AMI was the inaccurate early diagnosis, which resulted from the medical treatment might be a delay. Therefore, it is crucial to achieve the rapid detection of AMI. The cardiac troponin I (cTnI) level in human serum may significantly increase as the myocardial membrane ruptured, and the creatine kinase-MB (CK-MB) was also associated with the AMI recurrence and the infarct size of myocardial infarction. Both of them are regarded as important cardiac biomarkers for the early diagnosis of AMI. Therefore, we chose these two cardiac biomarkers as indicators for simultaneous detection. We proposed a single-track finger-pump microfluidic chip for simultaneous surface-enhanced Raman scattering (SERS) detection of cTnI and CK-MB. The entire detection process takes only 5 min without the cumbersome syringe pump. Meanwhile, it enables multiple reagent additions and removals of the unbonded reactants. This microfluidic sensor employed "sandwich" immunoassays based on SERS nanoprobes, AMI biomarkers, and magnetic beads. It is possible to detect two cardiac biomarkers simultaneously in a single measurement, greatly simplifying the detection process and reducing the detection time. Magnetic beads with SERS nanoprobes were separated and captured in the microchamber by a round magnet integrated into the chip. Our results showed that the detection limits of cTnI and CK-MB could reach to 0.01 ng mL−1, respectively. The limit of detections (LODs) match with the clinical threshold values for AMI biomarkers. It is believed that the proposed single-track finger-pump microfluidic chip can be used as an effective tool for determining early AMI.

Candidate genes and their alternative splicing may be potential biomarkers of acute myocardial infarction: a study of mouse model

BackgroundAcute myocardial infarction (AMI) is one of the leading causes of death in human being, and an effective diagnostic biomarker is still lacking. Whilst some gene association with AMI has been identified by RNA sequencing (RNA-seq), the relationship between alternative splicing and AMI is not clear.MethodsWe retrieved myocardial tissues within 24 h from mice with induced AMI and sham, and analysed the differentially expressed genes (DEGs) and differential alternative splicing genes (DASGs) by RNA-seq. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein interaction network analysis were performed on DEGs-DASGs-overlap genes. PCR was used to verify the expression levels of representative genes and alternative splicing in myocardial tissues of AMI and sham mice.Results1367 DEGs were identified, including 242 up-regulated and 1125 down-regulated genes, among which there were 42 DASGs. GO analysis showed that the cellular component was primarily enriched in plasma membrane, cell membrane integrity and extracellular region. The molecular function was enriched in protein binding and metal ion binding. The biological process was primarily enriched in cell adhesion, immune system process and cell differentiation. KEGG analysis showed the enrichment was mainly in JAK-STAT and PI3K-AKT signalling pathway. Postn, Fhl1, and Fn1 were low-expressed while Postn alternative splicing was high-expressed in myocardial tissue of AMI mice, which was consistent with sequencing results.ConclusionsThe pathogenesis of AMI involves differentially expressed genes and differential alternative splicing. These differentially expressed genes and their alternative splicing, especially, Fhl1, Fn1 and Postn may become new biomarkers of AMI.

Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction.

Ferroptosis is a form of regulatory cell death (RCD) caused by iron-dependent lipid peroxidation. The role of ferroptosis in the process of acute myocardial infarction (AMI) is still unclear and requires further study. Therefore, it is helpful to identify ferroptosis related genes (FRGs) involved in AMI and explore their expression patterns and molecular mechanisms. The AMI-related microarray datasets GSE66360 and GSE61144 were obtained using the Gene Expression Omnibus (GEO) online database. GO annotation, KEGG pathway enrichment analysis and Protein-protein interaction (PPI) analysis were performed for the common significant differential expression genes (CoDEGs) in these two datasets. The FRGs were obtained from the FerrDb V2 and the differentially expressed FRGs were used to identify potential biomarkers by receiver operating characteristic (ROC) analysis. The expression of these FRGs was verified using external dataset GSE60993 and GSE775. Finally, the expression of these FRGs was further verified in myocardial hypoxia model. A total of 131 CoDEGs were identified and these genes were mainly enriched in the pathways of "inflammatory response," "immune response," "plasma membrane," "receptor activity," "protein homodimerization activity," "calcium ion binding," "Phagosome," "Cytokine-cytokine receptor interaction," and "Toll-like receptor signaling pathway." The top 7 hub genes ITGAM, S100A12, S100A9, TLR2, TLR4, TLR8, and TREM1 were identified from the PPI network. 45 and 14 FRGs were identified in GSE66360 and GSE61144, respectively. FRGs ACSL1, ATG7, CAMKK2, GABARAPL1, KDM6B, LAMP2, PANX2, PGD, PTEN, SAT1, STAT3, TLR4, and ZFP36 were significantly differentially expressed in external dataset GSE60993 with AUC ≥ 0.7. Finally, ALOX5, CAMKK2, KDM6B, LAMP2, PTEN, PTGS2, and ULK1 were identified as biomarkers of AMI based on the time-gradient transcriptome dataset of AMI mice and the cellular hypoxia model. In this study, based on the existing datasets, we identified differentially expressed FRGs in blood samples from patients with AMI and further validated these FRGs in the mouse time-gradient transcriptome dataset of AMI and the cellular hypoxia model. This study explored the expression pattern and molecular mechanism of FRGs in AMI, providing a basis for the accurate diagnosis of AMI and the selection of new therapeutic targets.

Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction.

The occurrence of cardiovascular adverse events in the first year after ST-acute myocardial infarction (STEMI) remains high; therefore, identification of patients with poor prognosis is essential for early intervention. This study aimed to evaluate the prognostic value of metabolomics-based biomarkers in STEMI patients and explore their functional mechanisms. Metabolite profiling was performed using nuclear magnetic resonance. The plasma concentration of Kynurenine (Kyn) was measured using ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry. Major adverse cardiac and cerebral events were assessed for 1 year. A functional metabolomics strategy was proposed for investigating the role of Kyn in both vitro and vivo models. The adjusted hazard ratios in STEMI patients for Kyn in the 4th quartile 7.12(5.71-10.82) was significantly higher than that in the 3rd quartile 3.03(2.62-3.74), 2nd quartile 1.86(1.70-2.03), and 1st quartile 1.20(0.93-1.39).The incidence of MACCE was significantly different among Kyn quartiles and the highest incidence of MACCE was observed in the 4th quartile when compared with the 1st quartile (9.84% vs.2.85%, P<0.001).Immunofluorescence staining indicated that indoleamine-pyrrole 2,3-dioxygenase (IDO1) was located in the CD68 positive staining area of thrombi from STEMI patients and Kyn was induced in the early phase after myocardial infarction. Kyn could trigger inflammation and oxidative stress of macrophage cells by activation of the Sirt3-acSOD2/IL-1β signaling pathway in vitro. Plasma Kyn levels were positively associated with the occurrence of STEMI. Kyn could induce macrophage cells inflammation and oxidative stress by activating the Sirt3-acSOD2/IL-1β pathway following myocardial ischemia injury. Kyn could be a robust biomarker for STEMI prognosis and reduction of Kyn could be beneficial in STEMI patients.

Cardiac troponin T as a postmortem biomarker for acute myocardial infarction

The diagnosis of acute myocardial infarction (AMI), especially within the first hours after onset of ischemia, poses a challenge to the forensic pathologist. During this time, the infarction is generally not visible macroscopically nor with routine histology. Whilst cardiac Troponin T (cTnT) is a well-established biomarker for AMI clinically, its use as a postmortem diagnostic tool is less conclusive, warranting further investigation. The aim of this study was to investigate the sensitivity and specificity of cTnT as a postmortem diagnostic marker of AMI and the impact of postmortem interval (PMI) and cardiopulmonary resuscitation (CPR) on cTnT-concentrations. Samples from 64 subjects, 15 AMI cases and 49 controls, were collected at the Department of Forensic Medicine in Stockholm and analyzed for cTnT: one femoral blood sample was taken at arrival of the body to the morgue, and again during autopsy. Pericardial fluid (PCF) was only collected during autopsy. Sensitivity and specificity for serum cTnT were calculated to be 86.7 %/67.3 % and for pericardial fluid 86.7 %/44.9 %. cTnT samples taken during autopsy were generally higher than samples taken upon arrival to the morgue. A CPR-dependent elevation in serum cTnT was noted (P = .005). With a cut off at 56 n/L, serum cTnT can be used to rule out AMI. The postmortem interval and CPR must be taken into consideration when interpreting postmortem cTnT.

Prognostic value of circulating microRNA-21-5p and microRNA-126 in patients with acute myocardial infarction and infarct-related artery total occlusion.

Cardiovascular disease, including acute myocardial infarction (AMI), is a major global cause of mortality and morbidity. Specificity and sensitivity limit the utility of classic diagnostic biomarkers for AMI. Therefore, it is critical to identify novel biomarkers for its accurate diagnosis. Cumulative studies have demonstrated that circulating microRNAs (miRs) participate in the pathophysiological processes of AMI and are promising diagnostic biomarkers for the condition. This study aimed to ascertain the diagnostic accuracy of circulating miR-21-5p and miR-126 used as biomarkers in patients with AMI and infarct-related artery total occlusion (IR-ATO) or infarct-related blood-vessel recanalization (IR-BVR). The expression of miR-21-5p and miR-126 was examined separately in 50 healthy subjects, 51 patients with IR-ATO AMI, and 49 patients with IR-BVR AMI using quantitative real-time polymerase chain reaction. When compared with the control group, the IR-ATO AMI group exhibited increased miR-21-5p (p < 0.0001) and miR-126 (p < 0.0001), and the IR-BVR AMI group exhibited increased miR-21-5p (p < 0.0001). However, there was no significant difference in miR-126 between the IR-BVR AMI and the control groups. A Spearman's correlation coefficient showed a strong correlation was found between miR-21-5p, miR-126, cardiac troponin-I, and creatine kinase isoenzyme in all three groups, while a receiver operating characteristic analysis revealed that miR-21-5p and miR-126 exhibited considerable diagnostic accuracy for IR-ATO AMI. Circulating miR-21-5p and miR-126 may be promising prognostic biomarkers for patients with AMI and IR-ATO.

Programmable Y-Shaped Probes with Proximity Bivalent Recognition for Rapid Electrochemiluminescence Response of Acute Myocardial Infarction.

Herein, an exogenous luminophore-free and disposable electrochemiluminescence (ECL) biosensor was established for rapid response of acute myocardial infarction (AMI) using programmable Y-shaped probes (Y-probes) with proximity bivalent recognition. Specifically, the indium tin oxide thin film coated glass electrode (ITO) was modified with urchin-like porous TiO2 microspheres (pTiO2 MSs), which could achieve strong and stable ECL in S2O82- solution due to the dual promoting effect of the coreaction accelerator pTiO2 MSs, exhibiting 2.7-fold higher ECL intensity in comparison with that of bare ITO. Moreover, the Y-probes as bivalent recognition elements containing two kinds of cardiac troponin I (cTnI, a biomarker of AMI) aptamers and a linker labeled with ferrocene (L-Fc) were designed to export a "signal off" mode. When the target cTnI was in the proximity of the Y-probes, the L-Fc was separated from the electrode surface due to the proximity recognition of cTnI and its aptamers, achieving the highly effective recovery of ECL, which allowed for a much more rapid detection of cTnI than the sandwich-type immunoassay. As a proof of concept, an exogenous luminophore-free and disposable ECL platform for rapid and sensitive monitoring of cTnI was obtained and displayed a desired linear range from 100 fg mL-1 to 100 ng mL-1 with a limit of detection (LOD) of 30.1 fg mL-1, which can be ingeniously expanded as a portable home tester with ECL biosensors developments.

Graphitic Carbon Nitride and IGZO Bio-FET for Rapid Diagnosis of Myocardial Infarction.

Acute myocardial infarction (AMI), commonly known as a heart attack, is a life-threatening condition that causes millions of deaths every year. In this study, a transistor-based biosensor is developed for rapid and sensitive detection of cardiac troponin-I (cTnI), a diagnostic biomarker of AMI. A biosensing technique based on a field effect transistor (FET), which uses indium gallium zinc oxide (IGZO) as an excellent semiconducting channel, is integrated with nanosheet materials to detect cTnI. Porous carbon nitride (PCN) decorated with gold nanoparticles (Au NPs) is used as a bridge between the solid-state device and the biorecognition element. We demonstrate that this biosensor is highly sensitive and has an experimental limit of detection of 0.0066 ng/mL and a dynamic range of 0.01 ng/mL–1000 ng/mL. This is the first report of a semiconducting metal oxide FET cardiac biomarker sensor combined with PCN for the detection of cTnI. The reported compact microsystem paves the way for rapid and inexpensive detection of cardiac biomarkers.

Identification of an 11 immune-related gene signature as the novel biomarker for acute myocardial infarction diagnosis.

This study explored the valuable immune gene signature for diagnosis of acute myocardial infarction (AMI). Three training gene expression datasets (GSE48060, GSE34198, and GSE97320) and one validation dataset (GSE109048) were downloaded from GEO database. The differentially infiltrated immune cells were analyzed by CIBERSORT. The immune genes were screened by WGCNA with differential immune cells as phenotype. Differentially expressed genes were analyzed in training datasets, followed by differential immune gene identification. The immune genes with diagnostic value were filtered by univariate regression analysis and LASSO model construction. ROC curve evaluated the diagnostic value of this model. A total of 304 differential immune genes were obtained, which were closely related to immune response-related pathways. An 11-gene signature (ADAMTS1, CNN2, DHRS13, DUSP1, FASLG, GNPTAB, NARF, PHC2, RAB7A, VNN3, and YIPF3) was filtered to be diagnostic biomarker for AMI (AUC = 0.805) and validated in GSE109048 dataset (AUC = 0.608). Based on the diagnostic model, high- and low-risk groups showed ten differential immune cells (such as T cells gamma delta, Macrophages M0, and Neutrophils) and differentially activated immune pathways (such as Antigen_Processing_and_Presentation and Cytokine_Receptors). PHC2 showed the highest positive correlation with Neutrophils and Cytokine_Receptors. The 11-gene signature could be served as a novel biomarker for the presence of AMI.

Fe2O3@SiO2@Eu-MOF@Tb-MOF Core/Multishell Nanoparticles for the Fluorescence Sensing of Aspirin and Acute Myocardial Infarction Biomarkers

As a dangerous cardiovascular disease, acute myocardial infarction (AMI) has taken the lives of countless patients. Symptom onset of AMI is accompanied by a high amount of AMI biomarkers, including creatine kinase isoenzyme (CK-MB), troponin I (CTn I), and myoglobin (Mb). On the other hand, aspirin is an effective curing drug for AMI. Herein, we applied the layer-by-layer (LBL) synthesis strategy to form stratified magnetic core/multishell lanthanide metal–organic framework (Ln-MOF) Fe2O3@SiO2@Eu-MOF@Tb-MOF (MagMOF) nanoballs. Further, target mRNA sequence and antibodies (NH2-mRNA, anti-CTn, and anti-Mb) for AMI biomarkers are combined with MagMOF, respectively. They can be utilized as a hybrid sensing platform for the detection of CK-MB, Mb, and CTn I with high sensitivity (the limit of detection (LOD) for CK-MB is 174.98 U L–1, for CTn I is 0.16 mg L–1, and for Mb is 0.94 mg L–1). The detection ranges of MagMOF toward CK-MB, Mb, and CTn I in human serum have covered their maximum normal range in the human body, respectively. Further, MagMOF was applied in the ratiometric detection of aspirin with high sensitivity and low limit detection (LOD = 0.43 μM). As a result, MagMOF is the first example of realizing stable, susceptible, fast, and convenient detection of these AMI biomarkers and curing drug aspirin.

Circulating cell-free micro-RNA as biomarkers: from myocardial infarction to hypertension.

MicroRNA (miRNA) are small, single strand non-coding RNA molecules involved in the post-transcriptional regulation of target genes. Since their discovery in 1993, over 2000 miRNAs have been identified in humans and there is growing interest in both the diagnostic and therapeutic potential of miRNA. The identification of biomarkers for human disease progression remains an active area of research, and there is a growing number of miRNA and miRNA combinations that have been linked to the development and progression of numerous cardiovascular diseases, including hypertension. In 2010, Chen et al. reported in Clinical Science that cell-free circulating miRNA could serve as novel biomarkers for acute myocardial infarction [1]. In this commentary, we expand on this topic to discuss the potential of using miRNA as biomarkers for hypertension and hypertension-related end-organ damage.

Higher serum phosphorus and calcium levels provide prognostic value in patients with acute myocardial infarction.

BackgroundAlthough traditional cardiovascular risk factors are closely related to the poor prognosis of acute myocardial infarction (AMI) patients, there are few studies on the relationship of serum phosphorus and calcium with prognosis in AMI patients. The relationship of serum phosphorus and calcium with prognostic biomarkers in AMI remains unclear.Methods and resultsA total of 3,891 AMI patients were enrolled from a prospective cohort study. We investigated the association of serum phosphorus and calcium with prognostic biomarkers. The risk of in-hospital heart failure (HF), post-discharge HF, all-cause mortality and cardiac mortality was estimated across quartiles of serum phosphorus and calcium levels. Serum phosphorus and calcium levels were associated with biomarkers of prognosis. Overall, 969 patients developed in-hospital HF during hospitalization, 549 patients developed post-discharge HF during a median follow-up of 12 months, and 252 patients died, with 170 cardiac deaths since admission. In the fully adjusted model, compared with patients in quartile 2 (Q2), patients with serum phosphorus levels in Q4 were at greater risk of post-discharge HF [sub-distributional hazard ratios (SHR) 1.55; 95% confidence interval (CI), 1.21–1.99], in-hospital HF [odds ratio (OR) 1.84; 95% CI, 1.47–2.31], all-cause mortality (HR 1.59; 95% CI, 1.08–2.32), and cardiac mortality (SHR 1.68; 95% CI, 1.03–2.75). Compared with patients in Q2, patients with corrected calcium levels in Q4 had a higher risk of in-hospital HF (OR 1.62; 95% CI, 1.29–2.04), all-cause mortality (HR 1.99; 95% CI, 1.37–2.88), and cardiac mortality (SHR 1.87; 95% CI, 1.19–2.96; all p-trend < 0.05).ConclusionSerum phosphorus and calcium levels were associated with AMI prognostic biomarkers in AMI. Higher serum phosphorus was independently related to the increased risk of in-hospital HF, postdischarge HF, all-cause mortality and cardiac mortality, and higher serum calcium was independently related to the increased risk of in-hospital HF, all-cause mortality and cardiac mortality after AMI.