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1.
Gene ; 836: 146670, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35714796

RESUMO

The goal of this study was to compare the global gene expression profile in cardiac tissues of pig infected with porcine circovirus 2 (PCV2) to that of healthy cells. Since PCV2 infection causes severe cardiovascular lesions, the myocardial tissue model was chosen for this study. In High-throughput transcriptome analysis, DESeq2 and CLC genomics workbench analyses revealed a total of 196 significantly differentially expressed genes (DEGs) (p-value < 0.05). Furthermore, 194 transcripts were upregulated, while only two were downregulated (HSPA6 and DNAJA1), with fold changes ranging from 16.293 to -10.002. Among the KEGG canonical pathways targeted by the DEGs in the functional analysis, adrenergic signalling in cardiomyocytes, Cardiac Muscle Contraction, Hypertrophic Cardiomyopathy (HCM), and Dilated Cardiomyopathy (DCM) tends to be enriched. The differentially expressed highly connected (DEHC) biomarker genes in pathogenicity of PCV2 infection, such as LDB3, MYOZ2, CASQ2, TNNT2, MLC2V, MYBPC3, ACTC1, TCAP, TNNI3, TRDN, CSRP3, MYL3, RYR2, LMOD2, MYH7, etc., were identified using protein-protein interaction (PPI) network analysis. The study might provide detailed information on the dysregulated genes and biological pathways in infected myocardial tissues that may be essential for PCV2-related heart pathology.

2.
Transpl Int ; 35: 10362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755856

RESUMO

Cardiac troponin is well known as a highly specific marker of cardiomyocyte damage, and has significant diagnostic accuracy in many cardiac conditions. However, the value of elevated recipient troponin in diagnosing adverse outcomes in heart transplant recipients is uncertain. We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020. We generated summary sensitivity, specificity, and Bayesian areas under the curve (BAUC) using bivariate Bayesian modelling, and standardised mean differences (SMDs) to quantify the diagnostic relationship of recipient troponin and adverse outcomes following cardiac transplant. We included 27 studies with 1,684 cardiac transplant recipients. Patients with acute rejection had a statistically significant late elevation in standardised troponin measurements taken at least 1 month postoperatively (SMD 0.98, 95% CI 0.33-1.64). However, pooled diagnostic accuracy was poor (sensitivity 0.414, 95% CrI 0.174-0.696; specificity 0.785, 95% CrI 0.567-0.912; BAUC 0.607, 95% CrI 0.469-0.723). In summary, late troponin elevation in heart transplant recipients is associated with acute cellular rejection in adults, but its stand-alone diagnostic accuracy is poor. Further research is needed to assess its performance in predictive modelling of adverse outcomes following cardiac transplant. Systematic Review Registration: identifier CRD42021227861.


Assuntos
Rejeição de Enxerto , Transplante de Coração , Adulto , Teorema de Bayes , Biomarcadores , Rejeição de Enxerto/diagnóstico , Transplante de Coração/efeitos adversos , Humanos , Troponina
3.
Talanta ; 249: 123649, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35688072

RESUMO

A "signal-off" Electrochemiluminescence (ECL) biosensing platform based on Glutathione-Au nanoclusters covered reduced graphene oxide (GSH-Au NCs@rGO) and Au nanoparticles functionalized copper oxide (Au@CuO) was fabricated. The GSH ligand protected Au NCs were spontaneously adsorbed on the rGO surface via Van der Waals force. As ECL emitters, GSH-Au NCs@rGO not only support more luminophores and immobilization of bioreceptor units also facilitates mass transfer, accelerating ECL excitation to obtain a higher ECL signal intensity. Remarkably, Au@CuO with good biocompatibility was first applied as a quenching probe. Au@CuO (acceptor)-dependent resonance energy transfers (RET) with GSH-Au NCs@rGO (donor) could effectively quenched the ECL intensity to a reasonable range for requirements of trace analysis. The proposed ECL biosensing platform was evaluated with cardiac troponin I (cTnI) as a model analyte, achieving a low detection limit of 54.95 fg/mL. This strategy may provide as new approaches for the sensitive detection of biomarkers in the early clinical diagnosis of diseases.

4.
Talanta ; 249: 123577, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35724555

RESUMO

A sensitive unlabeled ratiometric biosensor was developed to the detection of cardiac troponin I (cTnI). This biosensor was established by using the glassy carbon electrode coated with graphene oxide to form a platform bonded with N, Zn co-doped graphene quantum dots (N, Zn-GQDs). The N, Zn-GQDs was successfully prepared as the raw materials of graphite powder and characterized. Antibodies of cTnI were bonded to the surface of N, Zn-GQDs as the nanoprobe by amide bonds. The signals of electrochemiluminescence (ECL) and differential pulse voltammetry (DPV) were exposed to decrease in the presence of cTnI, which caused the signal substance to move farther away from the electrode. It was found that the immune complex layer attenuated the intensity of ECL and DPV which could be used as the good overall signal for determining concentration of cTnI. The ratiometric biosensor had a good response to cTnI with the detection limit is 4.59 pg L-1 in the concentration range of 10-106 pg L-1. The developed method was evaluated for the detection of cTnI in human serum, and the obtained results were consistent compared to the reference values obtained by hospital standard enzyme linked immunoassay (ELISA) with 9.09%-11.1% of RSD. Our findings suggested that this ratiometric biosensor could be used to the detection of cTnI in human serum with lower cost and higher sensitivity, it also might be better potential application prospect based on N, Zn-GQDs to detect other biomarkers.

5.
J Am Heart Assoc ; 11(12): e024717, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35699194

RESUMO

Background Several imaging parameters and biomarkers provide diagnostic and prognostic information for wild-type transthyretin amyloid cardiomyopathy. However, the relevance of these parameters and their association with cardiac amyloid load requires further substantiation. We aimed to elucidate the association of imaging parameters obtained using 99mTc-labeled pyrophosphate scintigraphy, cardiovascular magnetic resonance imaging, global longitudinal strain (GLS), and cardiac biomarkers with cardiac amyloid load in patients with wild-type transthyretin amyloid cardiomyopathy. Methods and Results Eighty-eight patients with wild-type transthyretin amyloid cardiomyopathy who underwent 99mTc-labeled pyrophosphate scintigraphy and cardiovascular magnetic resonance were retrospectively evaluated. Quantitative cardiac amyloid load was obtained from 61 patients after myocardial biopsy. Correlations were assessed using Pearson's correlation coefficient applied to medical record data. The mean heart to contralateral ratio, native T1, extracellular volume, and GLS were 1.91±0.36, 1419.4±56.4 ms, 56.5±13.6%, and -9.4±2.5%, respectively. Median high-sensitivity cardiac troponin T (hs-cTnT) and BNP (B-type natriuretic peptide) levels were 0.0478 (0.0334-0.0691) ng/mL and 213.8 (125.8-392.7) pg/mL, respectively. The mean cardiac amyloid load was 22.9±15.0%. The heart to contralateral ratio correlated significantly with native T1 (r=0.397), extracellular volume (r=0.477), GLS (r=0.363), cardiac amyloid load (r=0.379), and Ln (hs-cTnT) (r=0.247). Further, cardiac amyloid load correlated significantly with native T1 (r=0.509), extracellular volume (r=0.310), GLS (r=0.446), and Ln (hs-cTnT) (r=0.354). Compared with BNP, hs-cTnT levels better correlated with several imaging parameters and cardiac amyloid load. Conclusions Increased cardiac amyloid load correlated with increased 99mTc-labeled pyrophosphate positivity, native T1, extracellular volume, and hs-cTnT levels, and an impaired GLS, suggesting that imaging parameters and cardiac biomarkers may reflect histological and functional changes attributable to amyloid deposition in the myocardium.


Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Amiloide , Neuropatias Amiloides Familiares/complicações , Biomarcadores , Cardiomiopatias/complicações , Cardiomiopatias/etiologia , Difosfatos , Humanos , Pré-Albumina , Estudos Retrospectivos
6.
EJIFCC ; 33(1): 43-55, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35645696

RESUMO

Objective: An early rule in (high specificity and high PPV) and early rule out (high sensitivity and high NPV) is essential for diagnosing acute myocardial infarction (AMI) to provide better utilization of resources, cost-effectiveness, and to reduce mortality. Methods: Consecutive chest pain patients (n=80) with symptoms indicative of coronary artery disease reported to the emergency room within 6 hours after onset of symptoms. An alternate Dual Marker Approach (DMA; both Heart-type Fatty Acid Binding Protein (H-FABP) and High sensitive Troponin-I (hsTnI) at 0 h) was compared to the Double Sampling approach (DSA; hsTnI at 0 h and 3 h (ESC guidelines)). Results: If both biomarkers were increased (n=17; 77.5%: 11 STEMI and 6 NSTEMI) above their respective cut-off value (HFABP 6.3 ng/mL and hsTnI 20.24 ng/L) at presentation, AMI ensued (100% PPV). Also, if both the markers were below their respective cut-offs at presentation, AMI was safely ruled out (n=41; with only 1 false negative). However, among the patients with either of these markers above their respective cut-off at presentation (n=22), DSA was required to find remaining AMI cases (n=4). Overall, DMA stands best for rule out (sensitivity 95.5%, NPV 97.6%) while DSA is superior for rule in (98.2% specificity, 95.2% PPV). Conclusion: With the use of the proposed DMA, 58/80 (72.5%) patients with acute chest pain were reliably ruled in/ruled out for AMI at the presentation itself, while the remaining patients still required serial monitoring (DSA) for confirmation.

7.
Front Physiol ; 13: 902079, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694406

RESUMO

Striated muscle contraction is inhibited by the actin associated proteins tropomyosin, troponin T, troponin I and troponin C. Binding of Ca2+ to troponin C relieves this inhibition by changing contacts among the regulatory components and ultimately repositioning tropomyosin on the actin filament creating a state that is permissive for contraction. Several lines of evidence suggest that there are three possible positions of tropomyosin on actin commonly called Blocked, Closed/Calcium and Open or Myosin states. These states are thought to correlate with different functional states of the contractile system: inactive-Ca2+-free, inactive-Ca2+-bound and active. The inactive-Ca2+-free state is highly occupied at low free Ca2+ levels. However, saturating Ca2+ produces a mixture of inactive and active states making study of the individual states difficult. Disease causing mutations of troponin, as well as phosphomimetic mutations change the stabilities of the states of the regulatory complex thus providing tools for studying individual states. Mutants of troponin are available to stabilize each of three structural states. Particular attention is given to the hypertrophic cardiomyopathy causing mutation, Δ14 of TnT, that is missing the last 14 C-terminal residues of cardiac troponin T. Removal of the basic residues in this region eliminates the inactive-Ca2+-free state. The major state occupied with Δ14 TnT at inactivating Ca2+ levels resembles the inactive-Ca2+-bound state in function and in displacement of TnI from actin-tropomyosin. Addition of Ca2+, with Δ14TnT, shifts the equilibrium between the inactive-Ca2+-bound and the active state to favor that latter state. These mutants suggest a unique role for the C-terminal region of Troponin T as a brake to limit Ca2+ activation.

8.
Future Cardiol ; 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35678322

RESUMO

Aim: This study investigated the association between plasma levels of GDF-15, hs-cTnT and NT-proBNP and the presence of coronary artery disease (CAD) in stable patients referred for elective coronary angiography. Methods: The outcome of CAD was defined as an ordinal variable with 3 levels. The association between each biomarker and the outcome was tested using the Winell and Lindbäck method. Results: In unadjusted analysis of 252 patients, GDF-15 and hs-cTnT were associated with the presence and extent of CAD. In multivariate regression analysis including traditional risk factors, this association was no longer significant. Conclusion: NT-proBNP, GDF-15 and hs-cTnT plasma levels do not seem to improve the predictive ability of traditional risk factors for CAD in stable patients referred for coronary angiography.


This study aimed to look at a possible association between blood levels of three molecules (GDF-15, hs-cTnT and N-terminal pro B-type natriuretic peptide [NT-proBNP]) and the presence of coronary artery disease (CAD) in stable patients referred for coronary angiography. Three CAD degrees of severity were identified: no CAD, 1- or 2-vessel CAD and 3-vessel or left main CAD. The association between each of the three blood molecules and CAD was studied using a specific statistical method. In the 252 consecutive patients enrolled, the two molecules GDF-15 and hs-cTnT were significantly associated with the presence and extent of CAD, while NT-proBNP was not. However, when the statistical analysis was adjusted for the traditional risk factors of CAD (age, gender, smoking, diabetes, etc.), the association of GDF-15 and hs-cTnT with CAD was no longer significant. NT-proBNP, GDF-15 and hs-cTnT blood levels do not seem to be independent predictive tools for CAD in stable patients referred for coronary angiography.

9.
Adv Physiol Educ ; 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35759528

RESUMO

In the early 1950s Setsuro Ebashi was a graduate student at Tokyo University studying the biochemical models of muscle contraction. These models contracted in the presence of ATP but what caught his attention was that the models did not relax when ATP was exhausted. Ebashi decided in 1952 to attempt to elucidate the mechanism of muscle relaxation using these models. This decision started a journey that would lead him to be the first to propose the calcium concept of muscle contraction and relaxation in 1961. It was an unpopular theory with biochemists who refused to accept that anything as simple as an inorganic ion, Ca2+, could control anything as important as muscle contraction. Ebashi was convinced that he was correct. He proceeded to show that micromolar concentrations of Ca2+ activated contraction. He discovered the particulate nature of the ATP dependent relaxing factor (the sarcoplasmic reticulum) and determined that it acted by binding Ca2+ in 1961. Most notably, he discovered in 1966 the Ca2+ receptor in muscle troponin, which mediated Ca2+ control of contraction. Ebashi's discoveries were considered the most important in the muscle field since the 1950s. Ebashi had to overcome the doubt of the scientific community. This story is one of great scientific achievement against great odds and the emergence of Japanese muscle research onto the international scientific stage.

10.
Herz ; 2022 Jun 14.
Artigo em Alemão | MEDLINE | ID: mdl-35699750

RESUMO

The collective term acute coronary syndrome (ACS) encompasses ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). The latter comprises unstable angina pectoris and non-ST-segment elevation myocardial infarction (NSTEMI). The diagnosis of STEMI necessitates an immediate referral to cardiac catheterization. The diagnostics and management of NSTE-ACS are more challenging. The current guidelines of the European Society of Cardiology (ESC) for treatment of NSTE-ACS were published in 2020 and deal with the topics of diagnostics, risk stratification, antithrombotic treatment, invasive or non-invasive coronary diagnostics and long-term treatment. The focus of the guidelines is on the application of high-sensitivity cardiac troponin assay(hs-cTn) combined with verified diagnostic algorithms to enable a rapid triage decision (rule-in as possible NSTEMI or rule-out as NSTEMI excluded) in the emergency room or the chest pain unit.

11.
Molecules ; 27(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35684321

RESUMO

Rumex vesicarius (L.) is a folklore medicinal herb that has been used for centuries to cure cardiovascular diseases. The present work was carefully designed to ascertain the pharmacological basis for R. vesicarius's therapeutic efficacy in cardiovascular diseases, as well as the underlying mechanism. In the ex vivo investigation, the aqueous-methanolic leaf extract of R. vesicarius was shown to have endothelium-dependent vasorelaxant effects in rabbit aorta tissue preparations, and its hypotensive responses were quantified by pressure and force transducers coupled to the Power Lab Data Acquisition System. Furthermore, when rabbits were subjected to adrenaline-induced myocardial infarction, R. vesicarius demonstrated cardioprotective characteristics. In contrast to the intoxicated group, the myocardial infarction model showed lower ALP, CK-MB, CRP, LDH, ALT, troponin, and AST levels (p > 0.005-0.000), as well as edema, necrosis, apoptosis, inflammatory cell enrolment, and necrosis. R. vesicarius exhibited significant antioxidant activity and delayed noradrenaline-induced platelet aggregation. Its cardioprotective, anticoagulant, and vasorelaxant properties in both investigations (in vivo and ex vivo) are mediated through partial endothelium-dependent, NO and calcium channel blockade mediated vasorelaxation. The minimizing of adrenaline, oxidative stress, and tissue damage demonstrate its therapeutic efficacy in cardiovascular diseases.


Assuntos
Infarto do Miocárdio , Rumex , Animais , Cardiotoxicidade/tratamento farmacológico , Catecolaminas , Epinefrina , Infarto do Miocárdio/tratamento farmacológico , Necrose/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Coelhos , Vasodilatadores/farmacologia
12.
Heart Lung Circ ; 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35753985

RESUMO

BACKGROUND: Troponin positive chest-pain with unobstructed coronary arteries (TPCP-UCA), occurs in 6% of cases of patients presenting with acute coronary syndrome (ACS). Whilst TPCP-UCA patients are known to be younger with less cardiovascular risk factors when compared to obstructive coronary disease (MICAD), no validated methods exist to reliably delineate these two conditions prior to coronary angiography. METHODS: We analysed 142 patients with MICAD and 127 patients with TPCP-UCA from 2015 to 2019. Several key predetermined clinical, biochemical and electrocardiograph (ECG) parameters, as well as Global Registry of Acute Coronary Events (GRACE) score, were collected for all patients. All TPCP-UCA patients underwent cardiac magnetic resonance imaging (cMRI). RESULTS: Patients with TPCP-UCA were younger than MICAD (44 vs 68 yrs, p<0.01), and with less cardiac risk factors of hypertension (31% vs 68%, p<0.01), hypercholesterolaemia (23% vs 56%, p<0.01), diabetes (11% vs 45%, p<0.01), prior ischaemic heart disease (8% vs 42%, p<0.01) and smoking history (29% vs 50%, p<0.01). Peak troponin (MICAD 2,084.5 ng/L vs TPCP-UCA 847.0 ng/L, p=0.02), serial-to-initial troponin ratio (MICAD 13.5 vs TPCP-UCA 5.1, p<0.01), and peak-to-initial troponin ratio (MICAD 69.6 vs TPCP-UCA 14.0, p<0.01) were all higher in the MICAD group. GRACE scores were significantly different across the two cohorts (TPCP UCA 74 vs MICAD 106, p<0.01), with a receiver operator characteristic (ROC) curve statistic of 0.794 (95% CI 0.739-0.850). On ECG analysis, MICAD had greater prevalence and sum of ST depression (40% vs 19% p<0.01; 1.6 mm vs 0.44 mm, p<0.01) and T wave inversion (37% vs 17%, p<0.01), whilst TPCP-UCA had greater presence of PR depression (20% vs 3% p<0.01), and longer repolarisation (T wave peak to end 89 ms vs 83 ms, p=0.04; T wave peak to end/corrected QT 0.208 ms vs 0.193 ms, p=0.03). All TPCP-UCA patients underwent cMRI. Aetiology was found in 82% of cases, with the leading diagnosis being myocarditis (58%), followed by infarction (8%), whilst 18% had a normal cMRI. CONCLUSIONS: TPCP-UCA is an important differential for patients presenting with ACS, and has several key demographic, biochemical and electrocardiographic differences. The present findings are hypothesis generating, thus prospective studies are required to determine and validate potential clinical utility.

13.
Front Physiol ; 13: 892979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755445

RESUMO

Small molecule cardiac troponin activators could potentially enhance cardiac muscle contraction in the treatment of systolic heart failure. We designed a small molecule, RPI-194, to bind cardiac/slow skeletal muscle troponin (Cardiac muscle and slow skeletal muscle share a common isoform of the troponin C subunit.) Using solution NMR and stopped flow fluorescence spectroscopy, we determined that RPI-194 binds to cardiac troponin with a dissociation constant KD of 6-24 µM, stabilizing the activated complex between troponin C and the switch region of troponin I. The interaction between RPI-194 and troponin C is weak (KD 311 µM) in the absence of the switch region. RPI-194 acts as a calcium sensitizer, shifting the pCa50 of isometric contraction from 6.28 to 6.99 in mouse slow skeletal muscle fibers and from 5.68 to 5.96 in skinned cardiac trabeculae at 100 µM concentration. There is also some cross-reactivity with fast skeletal muscle fibers (pCa50 increases from 6.27 to 6.52). In the slack test performed on the same skinned skeletal muscle fibers, RPI-194 slowed the velocity of unloaded shortening at saturating calcium concentrations, suggesting that it slows the rate of actin-myosin cross-bridge cycling under these conditions. However, RPI-194 had no effect on the ATPase activity of purified actin-myosin. In isolated unloaded mouse cardiomyocytes, RPI-194 markedly decreased the velocity and amplitude of contractions. In contrast, cardiac function was preserved in mouse isolated perfused working hearts. In summary, the novel troponin activator RPI-194 acts as a calcium sensitizer in all striated muscle types. Surprisingly, it also slows the velocity of unloaded contraction, but the cause and significance of this is uncertain at this time. RPI-194 represents a new class of non-specific troponin activator that could potentially be used either to enhance cardiac muscle contractility in the setting of systolic heart failure or to enhance skeletal muscle contraction in neuromuscular disorders.

14.
IJID Reg ; 2: 191-197, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35721427

RESUMO

Background: Data on biochemical markers and their association with mortality rates in patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in sub-Saharan Africa are scarce. An evaluation of baseline routine biochemical parameters was performed in COVID-19 patients admitted to the ICU, in order to identify prognostic biomarkers. Methods: Demographic, clinical, and laboratory data were collected prospectively from patients with PCR-confirmed COVID-19 admitted to the adult ICU of a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and the receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results: A total of 82 patients (median age 53.8 years, interquartile range 46.4-59.7 years) were enrolled, of whom 55 (67%) were female and 27 (33%) were male. The median duration of ICU stay was 10 days (interquartile range 5-14 days); 54/82 patients died (66% case fatality rate). Baseline lactate dehydrogenase (LDH) (adjusted relative risk 1.002, 95% confidence interval 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (adjusted relative risk 1.0004, 95% confidence interval 1.0001-1.0007; P = 0.014) were both found to be independent risk factors of a poor prognosis, with optimal cut-off values of 449.5 U/l (sensitivity 100%, specificity 43%) and 551 pg/ml (sensitivity 49%, specificity 86%), respectively. Conclusions: LDH and NT-proBNP appear to be promising predictors of a poor prognosis in COVID-19 patients in the ICU. Studies with a larger sample size are required to confirm the validity of this combination of biomarkers.

15.
Curr Issues Mol Biol ; 44(3): 1376-1394, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35723315

RESUMO

Cardiac troponins (cTns) have long been the most valuable and specific biomarkers for detecting ischemic myocardial cells (MCs) injury, which is one of the key signs of myocardial infarction (MI). Modern methods (highly sensitive and ultra-sensitive immunoassays (hs-cTns)) of detection are an important and indispensable tool for the early diagnosis of MI and the choice of patient management protocols. Timely diagnosis of MI can significantly improve the prognosis of patients. However, in real clinical practice, doctors often face a significant problem when using cTns-the difficulty of differential diagnosis due to frequent and unexplained increases in the concentration of cTns in blood serum. In addition, there is conflicting information that may potentially affect the diagnostic capabilities and value of cTns: the influence of certain biological factors (diurnal rhythm, gender and age) on serum cTns levels; extra-cardiac expression of cTns; the possibilities of non-invasive diagnosis of MI; and other pathological conditions that cause non-ischemic injury to MCs. To solve these problems, it is necessary to concentrate on studying the metabolism of cTns. The review of our current knowledge about cTns metabolism consists of two parts. In this (first) part of the manuscript, the main stages of cTns metabolism are briefly described and the mechanisms of cTns release from MCs are considered in detail.

16.
Diagnostics (Basel) ; 12(6)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35741183

RESUMO

BACKGROUND: Biomarkers were correlated with mortality in critically ill COVID-19 patients. No prediction tools exist for noncritically ill COVID-19 patients. We aimed to compare the independent prognostic value of inflammation and cardiac biomarkers for post-acute COVID-19 patients and the 30-day mortality rate in noncritically ill COVID-19 patients, as well as the relation with the virus variant involved. METHODS: This observational cohort study was conducted at an emergency clinical hospital between 1 October 2020 and 31 December 2021. We included consecutive patients with biomarkers determined within 24 h of presentation, followed up at least 30 days postdischarge. RESULTS: Post-acute COVID-19 was diagnosed in 20.3% of the cases and the all-cause 30-day mortality rate was 35.1% among 978 patients infected with variants of concern. Neutrophil-to-lymphocyte ratio (1.06 [95%CI, 1.01-1.11], p = 0.015) and NT-pro BNP were correlated with 30-daymortality, while the monocyte-to-lymphocyte ratio (2.77 [95%CI, 1.10-6.94], p = 0.03) and NT-pro BNP (1.68 [95%CI, 1.00-2.84], p = 0.05) were correlated with post-acute COVID-19. High-sensitivity to troponin was associated with 30-day mortality (1.55 [95%CI, 1.00-2.42], p = 0.05). A Cox proportional-hazards model confirmed that NT-pro BNP was independently associated with mortality. NT-pro BNP remained independently associated with 30-day mortality during follow-up (1.29 [95%CI, 1.07-1.56], p = 0.007) after adjustment for confounders. CONCLUSION: Inflammation and cardiac biomarkers, determined upon admission and predischarge, in a cohort of hospitalized noncritically ill COVID-19 patients throughout successive pandemic waves, showed a predictive value for post-acute COVID-19 and 30-day mortality.

17.
Front Surg ; 9: 789954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747434

RESUMO

Background: There is a lack of evidence about the predictive role of serum cardiac troponin I (cTnI) on the long-term adverse outcomes of acute type B aortic dissection (aTBAD) patients after thoracic endovascular aortic repair (TEVAR). In this study, we identified whether cTnI was an independent risk factor of 5-year adverse outcomes for aTBAD patients after TEVAR. Methods: We reviewed consecutive aTBAD patients without previous heart disease who were admitted for TEVAR. The total study population was divided into the cTnI(+) group (≥0.03 ng/mL) and the cTnI(-) group (<0.03 ng/mL) according to the time-dependent receiver operating characteristic curve analysis. The differences in clinical characteristics, operative details and clinical outcomes were compared between the two groups. Results: There was no difference in age and male prevalence between the two groups. Compared with the cTnI(-) group, the incidence of chronic kidney disease was higher in patients with cTnI ≥0.03 ng/mL. In addition, the cTnI(+) group presented with more frequent premature beats and non-myocardial-infarction ST-T segment changes. In terms of laboratory examinations, white blood cell counts, neutrophil counts, serum D-dimer and serum fibrin degradation products showed an increase in the cTnI(+) group, while lymphocyte and platelet counts showed a decrease in these patients. Patients with elevated cTnI suffered from increased risks of 5-year aortic-related adverse events (hazard ratio, HR = 1.822, 95% confidence interval, CI: 1.094-3.035; p = 0.021) and all-cause mortality (HR = 4.009, 95% CI: 2.175-7.388; p < 0.001). Conclusion: Among aTBAD patients without previous heart disease, preoperative elevated cTnI identified patients at an increased risk of long-term adverse outcomes after TEVAR.

18.
Medicina (Kaunas) ; 58(6)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35744058

RESUMO

Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be characterized to elucidate the mechanisms of the pathogenesis of the diseases. As protein motions have a hierarchy ranging from local side-chain motions, through segmental motions of loops or disordered regions, to diffusive motions of entire molecules, segmental motions, as well as local motions, need to be characterized. Materials and Methods: Combined analysis of quasielastic neutron scattering (QENS) spectra with the structural data provides information on both the segmental motions and the local motions of the IDPs/IDRs. Here, this method is applied to re-analyze the QENS spectra of the troponin core domain (Tn-CD), various mutants of which cause the pathogenesis of familial cardiomyopathy (FCM), and α-synuclein (αSyn), amyloid fibril formation of which is closely related to the pathogenesis of Parkinson's disease, collected in the previous studies. The dynamical behavior of wild-type Tn-CD, FCM-related mutant Tn-CD, and αSyn in the different propensity states for fibril formation is characterized. Results: In the Tn-CD, the behavior of the segmental motions is shown to be different between the wild type and the mutant. This difference is likely to arise from changes in the intramolecular interactions, which are suggested to be related to the functional aberration of the mutant Tn-CD. In αSyn, concerted enhancement of the segmental motions and the local motions is observed with an increased propensity for fibril formation, suggesting the importance of these motions in fibril formation. Conclusions: Characterization of the segmental motions as well as the local motions is thus useful for discussing how the changes in dynamical behavior caused by the disease-related mutations and/or environmental changes could be related to the functional and/or behavioral aberrations of these proteins.


Assuntos
Proteínas Intrinsicamente Desordenadas , Doença de Parkinson , Difusão , Humanos , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Nêutrons , Doença de Parkinson/metabolismo
19.
Injury ; 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35750532

RESUMO

BACKGROUND: Cardiac troponin I (cTnI) levels are usually measured in primary evaluations of blunt cardiac injury (BCI) patients. We evaluated the associations of cTnI levels with the outcomes of BCI patients at different times. METHODS: From 2015 to 2019, blunt chest trauma patients with elevated cTnI levels were compared with patients without elevated cTnI levels using propensity score matching (PSM) to minimize selection bias. The cTnI levels at different times in the survivors and nonsurvivors were compared. RESULTS: A total of 2,287 blunt chest trauma patients were included, and 57 (2.5%) of the patients had BCIs. PSM showed that patients with and without elevated cTnI levels had similar mortality rates (13.0% vs. 11.1%, p-value = 0.317], hospital lengths of stay (LOSs) [17.3 (14.4) vs. 15.5 (22.2) days, p-value = 0.699] and intensive care unit (ICU) LOSs [7.7 (12.1) vs. 6.4 (15.4) days, p-value = 0.072]. Among the BCI patients, nonsurvivors had a significantly higher highest cTnI level during the observation period than survivors. Additionally, patients who needed surgical intervention had significantly higher highest cTnI levels than patients who did not. CONCLUSIONS: An elevated cTnI level is insufficient for the evaluation of BCI and the determination of the need for further treatment. The highest cTnI level during the observation period may be related to mortality and the need for surgery in BCI patients.

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