Kinase Isoenzyme MB Research Articles

Exercise training combined with alprostadil improves myocardial infarction and coronary microcirculation disorder in aged rats by inhibiting mitogen-activated protein kinase (MAPK) signaling pathway activation.

We aimed to explore the effects and mechanisms of exercise training combined with alprostadil (ALPR) treatment on myocardial infarction (MI) in aged rats. Male Wistar rats were randomly divided into five groups. One day after MI induction, an automatic biochemical analyzer was used to measure cardiac troponin I (cTnI), cardiac troponin T (cTnT), and creatine kinase MB isoenzyme (CK-MB) serum levels. One week after MI induction, echocardiography was performed to examine the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fraction shortening (LVFS) rates of the rats. Parameters such as body weight (BW), heart mass index, and the heart weight (HW)/tibia length (TL) ratio of the rats were also calculated. Western blot was performed to assess angiogenesis and mitogen-activated protein kinase (MAPK) signal-related protein expression. Compared with the MI group, the LVEDD and LVESD in the Trained + ALPR group were significantly decreased, while LVEF, LVFS, HW/BW, and HW/TL were significantly increased. Additionally, the Trained + ALPR group exhibited decreased levels of cTnI, cTnT, and CK-MB and significantly reduced MI size and myocardial injury. Moreover, compared with the Trained or ALPR group, the Trained + ALPR group showed upregulated energy metabolism, increased microvessel density, and better efficacy. Finally, the Trained + ALPR group showed a significant increase in angiogenesis-related proteins and a significant reduction in MAPK signaling pathway-related protein activity. Exercise training combined with ALPR improved MI in elderly rats by inhibiting MAPK signaling, promoting angiogenesis, and increasing metabolism.

Abamectin causes cardiac dysfunction in carp via inhibiting redox equilibrium and resulting in immune inflammatory response and programmed cell death.

This study aims to investigate the effects of environmentally relevant concentrations of abamectin on the cardiac function of carp and the potential mechanisms. Here, male carp were exposed to abamectin, and cardiac function-related enzymatic markers were examined. Cardiac histopathology, redox equilibrium, inflammation, and cell death were evaluated. Abamectin exposure caused cardiac dysfunction by upregulating lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK), creatine Kinase MB isoenzyme (CK-MB) and white blood cells (WBCs), and decreasing red blood cells (RBCs) and hemoglobin (Hb). DHE staining and biochemical assays revealed that abamectin caused ROS release and oxidative stress by inhibiting Nrf2-ARE pathway. Histopathological and real-time fluorescence quantitative PCR (RT-qPCR) assays revealed that abamectin caused myocardial fiber swelling and inflammatory cell infiltration, enhanced pro-inflammatory cytokines tumor necrosis factor-α (Tnf-α), interleukin-1 beta (Il-1β), and Il-6 levels and attenuated anti-inflammatory cytokines Il-10 and transforming growth factor beta 1 (Tgf-β1) through activating NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa-B (NF-κB) pathway. Tunel staining showed that abamectin triggered cardiac apoptosis via activating p53-mediated mitochondrial apoptosis with elevated bcl2-associated X (Bax), reduced B-cell lymphoma-2 (Bcl-2), and activated Caspase-9 and Caspase-3. Immunoblot analysis revealed that abamectin activated autophagic flow by inhibiting mammalian target of rapamycin (mTOR), resulting in the conversion of LC3B from LC3-I to LC3-II, elevation of autophagy protein 5 (Atg5), and reduction of p62. Overall, abamectin caused cardiac dysfunction in carp via inhibiting redox equilibrium and resulting in immune inflammatory response and programmed cell death.

Coxsackievirus A6 was the most common enterovirus serotype causing hand, foot, and mouth disease in Shiyan City, central China.

Hand, foot, and mouth disease (HFMD) has become one of the most common infectious diseases in China. Before 2016, the primary causal serotypes were enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Following the introduction of EV-A71 vaccines in China since 2016, the situation could change. CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China. However, the epidemiological characteristics of central China remain unknown. To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City, central China, in recent years. The epidemiological, clinical, and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed. 196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020. To detect and genotype enteroviruses, real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used. In Shiyan, 168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes. Based on the logistic regression model, the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan. From 2016 to 2020, 35840 HFMD cases were reported in Shiyan. The number of cases decreased by 48.4% from 2016 to 2017. Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year, respectively. In 2020, a decrease of about 85.5% was reported when compared to 2019. The most common serotypes shifted from EV-A71 and CV-A16 (about 60%-80% in 2016 and 2018) to others (more than 80.0% in 2017, 2019, and 2020). EV-A71 lost its dominance in 2017 in Shiyan. Among 196 confirmed HFMD cases, 85.7% tested positive for enterovirus, with CV-A6 being the most common serotype (121/168, 72.0%). The positive rates for CV-A16 and CV-A10 were 4.8% and 3.0%, respectively. There was no EV-A71 discovered. Infection with CV-A6 was linked to fever, myocardial damage, increased creatine kinase MB isoenzyme, and lactate dehydrogenase levels. CV-A6 was the most common enterovirus serotype in Shiyan City, replacing EV-A71 and CV-A16 as the HFMD pathogen. Developing vaccines against CV-A6 or multiple pathogens, as well as rising CV-A6 surveillance, will help prevent HFMD in central China.

Myocardial protective effect of sivelestat sodium in rat models with sepsis-induced myocarditis.

The incidence of sepsis has been steadily increasing worldwide, and the heart is one of the target organs that can be easily damaged by sepsis. At present, antibiotics and organ function support are the main treatment options for sepsis and multiple system organ dysfunction, but are still under investigation. Fifty rats were randomly divided into the sham operation group, sepsis group, sivelestat sodium low-dose (L) group (administered with sivelestat sodium 1.6 mg/kg), sivelestat sodium middle-dose (M) group (administered with sivelestat sodium 4.8 mg/kg), and sivelestat sodium high-dose (H) group (administered with sivelestat sodium 10 mg/kg). Morphological changes of myocardial cells and the distribution of extracellular signal-regulated kinase (ERK)1/2 proteins were observed by light microscope. Serum troponin-T, creatine kinase isoenzyme MB, brain natriuretic peptide, interleukin (IL)-6, tumor necrosis factor-α, and IL-1β levels and changes in cardiac function indicators were measured. The protein expressions of Bax, Bcl-2, and ERK1/2 were detected by Western blotting. Compared with the sham operation group, the release of inflammatory factors in the sepsis group increased; the protein expressions of Bax, Bcl-2, and ERK1/2 increased; left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximum rate of LVP rise (+dp/dtmax) level decreased, whereas -dp/dtmax increased. In the sivelestat sodium groups, the release of inflammatory factors decreased; Bax expression decreased, whereas Bcl-2 and ERK1/2 protein expressions increased; LVSP, LVEDP, and +dp/dtmax increased, whereas -dp/dtmax decreased. In addition, all of these changes occurred in a dose-dependent manner. Sivelestat sodium can effectively lower the expressions of inflammatory factors and improve cardiac function. It can act on the ERK1/2 signaling pathway to exert its cardiomyocyte-protective effect, and the activation of this signaling pathway can offer potential treatment sites for septic myocarditis.

High levels of cardiovascular biomarkers in fatal Chikungunya virus infection

Chikungunya virus (CHIKV) infection is an emerging arboviral disease that has spread geographically to many previously unaffected areas. Although severe cases of acute CHIKV infection have been documented, little is known about its pathogenesis. We aimed to determine the levels of cardiovascular biomarkers in fatal and non-fatal patients with acute CHIKV infection. This study included fatal and non-fatal patients with CHIKV reported to National System for Public Health Surveillance and laboratory-confirmed by the Colombian National Institute of Health. Each fatal patient was matched to 2 non-fatal patients for age (± 10 years). Blood samples were processed for cardiovascular biomarkers by multiplex immunoassays. Twenty-five cases of fatal CHIKV infection and 50 patients of non-fatal CHIKV infection were included. Nearly 20% of the population were under 10 years old and 52% were over 60. The median serum levels of endocan-1 (p = 0.000), creatine kinase MB isoenzyme (p = 0.000), oncostatin (p = 0.000), fatty-acid-binding protein 3 (p = 0.000) and fatty-acid-binding protein 4 (p = 0.000) were significantly higher in fatal CHIKV infection cases than in non-fatal patients. Troponin I tended to be higher in fatal CHIKV infection cases than in non-fatal CHIKV infection patients (p = 0.063). Among fatal patients, no significant differences were found in serum levels of cardiovascular biomarkers among younger (< 50 years-old) and older (≥ 50 years-old) patients. We found high serum levels of cardiovascular biomarkers in fatal CHIKV infection. These results promote the fact that endothelial and cardiac damage can occurs and may be significant factors related organ failure and death in these patients.

Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Some patients with autism spectrum disorder (ASD) exhibit elevated serum creatine kinase levels, which are believed to be associated with mitochondrial dysfunction. Although a few articles have reported this situation in the past and the increase mostly ranges from 100 to 300 U/L, there is a paucity of previous study focusing on the serum creatine kinase MB isoenzyme. This article discusses a 5-year-old girl with ASD, whose serum creatine kinase and creatine kinase MB isoenzyme have been rising for nearly 2 years, fluctuating at 584–993 and 111–625 U/L respectively. Except for behavioral and language symptoms associated with ASD, the child appears normal in other aspects. The child's laboratory tests showed no abnormality, except that the serum levels of lactic acid was slightly higher than normal (1.89 mmol/L, normal 1.33–1.78 mmol/L). The child was prescribed with a traditional Chinese medicine during the process and the serum creatine kinase MB isoenzyme level decreased dramatically to 111 U/L after the treatment. This study firstly recorded the serum creatine kinase levels and the MB isoenzyme in patients with autism spectrum disorder for nearly 2 years, indicating that patients with ASD may experience long-term increases in serum creatine kinase and creatine kinase MB isoenzyme, and that the traditional Chinese medicine decoction Xinfukang can temporarily reduce the serum creatine kinase MB isoenzyme level in patients. Nevertheless, the effect is not sustained. Therefore, it is of great importance to conduct long-term longitudinal studies so as to elucidate the potential mechanism responsible for long-term elevation of serum creatine kinase level.

CD36 inhibition partially attenuates myocardial injury in diabetic rats with ischemic postconditioning

IntroductionTo investigate the role of CD36 (fatty acid translocation enzyme) in the myocardial ischemia reperfusion (IR) injury in diabetes with ischemic postconditioning (IPostC).Research design and methodsAdult male Sprague-Dawley rats received...

Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis.

BackgroundHand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CV-A6) has become prevalent in many parts of the world. It is commonly referred to as atypical HFMD which more likely to present as bullous lesions. Compared with traditional HFMD, its misdiagnosis rate is relatively high, which brings difficulties to clinical diagnosis. We retrospectively analyze the clinical characteristics of children with HFMD with bullous lesions caused by CV-A6.MethodsThe study included 68 children with atypical HFMD caused by CV-A6 who were hospitalized from 2018 to 2020. Data of the children including age, sex, month of HFMD onset, the morphologies and distribution of rashes, the details of fever, the presence or absence of onychomadesis, and laboratory test results were analyzed and compared between an infant group (<1 year), a toddler group (1–<3 years), and a preschool group (3–<6 years).ResultsOf the 68 children, 67 were younger than 5 years old, with a male to female ratio of 1.62:1. The disease peaked in the period from June to September. With 75.0% of the infant group had more than three kinds of rashes; 95.0% of the preschool group had rashes in more than five locations. These differences were statistically significant (P<0.05). All children had fever. The peak fever in the toddler group was lower (P=0.033). No critical cases were observed in any of the groups. Of the 61 children who were successfully followed up, 68.9% developed onychomadesis within 2–3 weeks. The proportion of cases with abnormal liver function was 83.3%, 41.7%, and 10.0% in the infant, toddler, and preschool groups (P<0.001). The proportion of cases with increased serum creatine kinase MB isoenzyme (CK-MB) were significantly higher in the toddler group (P<0.05).ConclusionsAtypical HFMD caused by CV-A6 infection usually occurred in children under 5 years old. The morphologies of the rashes in the infant group changed more, while the rashes in the preschool group was more widely distributed. The incidence of critical cases was low. More than half of the cases can develop onychomadesis in the recovery period. Organ damage was relatively mild in the preschool group.

Network Meta-analysis of traditional Chinese medicine injections against anthracycline-induced cardiac injury

This study aimed to systematically evaluate the effect of traditional Chinese medicine(TCM) injections on anthracycline-induced cardiac injury. The Cochrane Library, PubMed, EMbase, CNKI, and other databases were electronically retrieved to gather randomized controlled trials(RCTs) of TCM injections against anthracycline-induced cardiac injury from their inception to September 2021. After two research fellows independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed and network Meta-analysis was performed by R 4.1.0 and Stata 15.1. A total of 50 RCTs were included, involving eight TCM injections. Network Meta-analysis showed that:(1)the combination of anthracyclines with Huachansu Injection might be the optimal treatment to reduce the abnormal electrocardiogram.(2)The combination with Shenfu Injection might be the optimum treatment to ameliorate the left ventricular ejection fraction(LVEF) decrease.(3)The combination with Shenqi Fuzheng Injection might reduce the incidence of cardiotoxicity most satisfactorily.(4)The combination with Xinmailong Injection might improve the elevated cardiac troponin I(cTnI) optimally.(5)The combination with Shenmai Injection might be optimal to control the rise of creatine kinase MB isoenzyme(CK-MB).(6)The combination with Kushen Injection might be the regimen with the lowest gastrointestinal reactions. TCM injections had desirable effect on anthracycline-induced cardiac injury, with low incidence of adverse reactions, and each TCM injection had its own unique advantages. Due to the limitations in quality and methodological conduct of the included studies, more high-level RCTs are needed to validate the conclusions.

Simultaneous SERS-based immunoassay of dual cardiac markers on pump-free hybrid microfluidic chip

We developed a new pump-free hybrid microfluidic chip for the simultaneous SERS-based immunoassay of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin (cTnI) cardiac markers. As a main composition, the patterned SERS paper substrate was firstly fabricated by UV light curing method using water-based polyurethane acrylate resin to have the hydrophobic barriers of microchannel, and then in-situ synthesized AuNPs on hydrophilic paper microchannel. It took advantage of 3D fibre structure to provide the capillarity force and compact AuNPs deposition scaffold for sample flow and highly sensitive SERS detection. The paper substrate was attached to PDMS microchannel and enabled the aqueous samples to flow in PDMS microchannel, which driven by capillary force of paper materials. The proposed method successfully detected the concentrations of two cardiac markers ranging from 0.01 to 50 ng mL−1. These results reveal the simultaneous detection capability of SERS-based immunoassay on the pump-free hybrid microfluidic chip without heavy external pump. The integration of paper and PDMS microfluidic chip is portable, low-cost, and tremendously useful for the simultaneous detection of cardiac markers.

Serum TP53 Protein Level as a Sensitive Biomarker for the Diagnosis of Myocardial Damage in Children.

BackgroundHigh levels of TP53 protein can lead to apoptosis of myocardial cells. However, TP53 protein influence of myocardial damage remains unclear. This prospective study investigated the involvement of TP53 protein in secondary myocardial damage in children up to 18 years of age.Material/MethodsSerum TP53 protein, N-terminal prohormone B-type natriuretic peptide (NT-ProBNP), cardiac troponin-I (cTnI), and creatine kinase isoenzyme MB (CK-MB) concentrations were measured in 50 hospitalized patients with secondary myocardial damage, 50 hospitalized patients without myocardial damage, and 50 healthy individuals (control). Cardiac damage was diagnosed based on cTnI, NT-ProBNP, and CK-MB levels, with electrocardiographic evidence as the reference. The appropriate cut-off value of TP53 protein for secondary myocardial damage was analyzed by receiver operating characteristic (ROC) curves.ResultsThe serum TP53 protein, NT-ProBNP, cTnI, and CK-MB concentrations of the patients with and without myocardial damage were 10.20±1.20 and 0.30±0.10 ng/L, 505.30 and 107.8 ng/L, 0.23±0.13 and 0.02±0.01 μg/L, and 28.30±5.13 and 12.24±4.29 IU/L, respectively. For the 50 patients with myocardial damage, the area under the ROC curve for serum TP53 protein, NT-ProBNP, cTnI, and CK-MB concentrations were 0.89 (95% CI: 0.81–0.95), 0.83 (95% CI: 0.77–0.91), 0.92 (95% CI: 0.84–0.97), and 0.85 (95% CI: 0.78–0.93), respectively, and the diagnostic cut-off values were 12.00 ng/L, 500.00 ng/L, 0.16 μg/L, and 27.00 IU/L, respectively, with positive likelihood ratios of 20.8, 13.2, 24.6, and 15.6.ConclusionsTP53 protein is a valid biomarker of secondary myocardial damage in pediatric patients and can be diagnostic.

Cardiotoxicity Related to Immune Checkpoint Inhibitors: A Real-World Retrospective Analysis

BackgroundCardiotoxicity related to immune checkpoint inhibitors (ICIs) is a rare but potentially lethal. In ICI-associated adverse events, evidence of cardiotoxicity and clinical predictive factors related to ICI is lacking. Here, we aim to assess the incidence and predictive factors of cardiotoxicity related to ICIs in real-world practice.ObjectiveWe retrospectively analyzed consecutive patients who received PD-1 or PD-L1 at the First Affiliated Hospital of Xi'an Jiaotong University. Clinical characteristics and cardiac lesion markers were collected both at baseline and during longitudinal follow-up from the Biobank database. Follow-up CKMB and NT-proBNP levels and ratios were then evaluated.ResultsA total of 2,304 patients with either PD-1 or PDL-1 utilization between August 2018 and April 2021 were collected. The average age was 59.44 ± 11.45 among PD-1 inhibitor utilizer and 58.97 ± 12.16 among PDL-1 inhibitor utilizer. The baseline creatine kinase isoenzyme MB (CKMB) levels were 17 ± 19 U/L in PD-1 inhibitor users and 17 ± 23 U/L in PDL-1 inhibitor users. Majority of patients were male, with advanced stage cancer, and received ICIs as second-line therapy. The longitudinal change of cardiac enzymes and NT-pro BNP were collected. Cardiac lesion as defined by three times increase of CKMB happens in only minority of patients receiving ICIs therapy. It is also identified that increased CKMB happened in PD-1 inhibitor groups, but not PDL-1 inhibitor groups.ConclusionWe evaluated the profile of cardiotoxicities caused by ICIs based on real-world experience. The cardiac lesion markers are generally unaltered, but it appears that the increased CKMB happened in PD-1 inhibitor groups, but not PDL-1 inhibitor groups.

Inhibition of Nitrosative Stress Attenuates Myocardial Injury and Improves Outcomes after Cardiac Arrest and Resuscitation.

Nitrosative stress is widely involved in cell injury via inducing the nitration modification of a variety of proteins. This study aimed to investigate whether inhibition of nitrosative stress attenuated myocardial injury and improved outcomes in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Adult male Wistar rats were subjected to asphyxia-induced cardiac arrest and subsequently resuscitation. One minute after return of spontaneous circulation (ROSC), rats were randomized and administered the nitrosative stress inhibitor, FeTMPyP (1 or 3 mg/kg), or normal saline as a placebo. 3-Nitrotyrosine (3-NT), mean arterial pressure (MAP), heart rate (HR), mortality, electrocardiogram (ECG), left ventricular ejection fraction (EF) and fractional shortening (FS), and levels of myocardial apoptosis were evaluated. The concentrations of lactate, creatine kinase MB isoenzyme (CK-MB), and angiotensin II (Ang II), were measured in blood samples. 3-NT level was significantly increased in the heart after ROSC. Administration of FeTMPyP (1 or 3 mg/kg) attenuated the increase of 3-NT in the myocardium. Inhibition of nitrosative stress improved survival and attenuated CA/CPR-induced reperfusion injury by maintaining the stability of MAP and HR, and reducing the accumulation of lactic acid. Post-cardiac arrest rats had higher serum CK-MB and Ang II than healthy rats, while EF and FS were lower in healthy rats. Inhibition of nitrosative stress not only alleviated ischemic heart injury but also reduced the occurrence of CA/CPR-induced of arrhythmias. Moreover, nitrosative stress mediated the upregulation of Cleaved caspase-3 and downregulation Bcl-2, which was abolished by FeTMPyP. Inhibition of nitrosative stress is a novel molecular target to alleviate myocardial injury and improve outcomes in a rat model of CA/CPR.

Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway.

The present study aimed to evaluate the effects of hypercholesterolemia on cardioprotection of ischemic preconditioning and α7 nicotinic acetylcholine receptor (α7nAChR) agonist postconditioning and explore the potential mechanisms that hypercholesterolemia affected their cardioprotection. Hypercholesterolemic and normal rats were divided into the four groups that received the following treatments: i) Hypercholesterolemic control and normal control groups; ii) hypercholesterolemic ischemia/reperfusion (HI) and normal ischemia/reperfusion (NI) groups; iii) hypercholesterolemic ischemic preconditioning (HIPC) and normal ischemic preconditioning (NIPC) groups; and iv) hypercholesterolemic PNU282987 postconditioning (HPNU) and normal PNU282987 postconditioning (NPNU) groups. Serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels after ischemia/reperfusion were assayed. Furthermore, infarct size and expression levels of Akt, phosphorylated (p)-Akt and endothelial nitric oxide synthase (eNOS) in ischemic myocardium were assessed. Compared with the NI group, serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased, and myocardial p-Akt/Akt and eNOS/GAPDH ratios were significantly increased in the NIPC and NPNU groups. Compared with the HI group, serum CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased in the HIPC group; however, myocardial p-Akt/Akt and eNOS/GAPDH ratios did not significantly change in the HIPC group. Furthermore, there were no significant difference between the HI and HPNU groups in serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels, infarct size, myocardial p-Akt/Akt and eNOS/GAPDH ratios. In conclusion, hypercholesterolemia could aggravate myocardial ischemia/reperfusion injury, attenuate cardioprotection of ischemic preconditioning and eliminate cardioprotection from α7nAChR agonist postconditioning by enhancing inflammation and inhibiting PI3K/Akt/eNOS pathway.

Elevated Myoglobin in Patients With Primary Aldosteronism: A Cross-Sectional Study.

ObjectivesPrimary aldosteronism (PA) is characterized by the autonomous excessive production of aldosterone in the adrenal cortex. Aldosterone is associated with damages to heart muscle and skeletal muscle. The purpose of this study was to evaluate serum levels of muscle injury markers and their associated factors in patients with primary aldosteronism.MethodsWe retrospectively enrolled subjects with PA and essential hypertension (EH) who had completed testing for serum high sensitivity troponin T (hs-TnT), creatine kinase isoenzyme MB (CK-MB) and myoglobin from the database of the Chongqing Primary Aldosteronism Study (CONPASS). Univariate and multivariate linear regression analyses were performed to analyze the influencing factors of myocardial injury markers.ResultsIn total, 278 patients with PA and 445 patients with EH were enrolled in this study. Compared with EH patients, serum concentrations of hs-TnT [7.0 (4.0–12.0) vs. 6.0 (3.0–11.0) ng/L; p=0.005] and myoglobin [24.2 (21.0–38.1) vs. 21.8 (21.0–31.9) μg/L; p=0.023] were significantly higher among PA patients, while no significant difference of CK-MB was found between two groups [1.4 (1.0–2.0) vs. 1.3 (0.9–1.9) μg/L; p=0.154]. Univariate linear regression analysis showed that myoglobin was negatively correlated with serum potassium (β=-0.31; p<0.01) and positively correlated with plasma aldosterone concentration (β=0.40; p<0.01) in the PA group, while no significant correlation was found between hs-TnT and biochemical parameters. After adjusting for multiple confounders, myoglobin was negatively correlated with serum potassium (β=-0.15; p<0.05) and positively correlated with plasma aldosterone concentration (β=0.34; p<0.01) in the PA group.ConclusionsThe serum level of myoglobin was significantly increased in PA patients, and myoglobin was independently correlated with plasma aldosterone concentration.

MiR-24-3p Attenuates Doxorubicin-induced Cardiotoxicity via the Nrf2 Pathway in Mice.

The nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is associated with doxorubicin (DOX)-induced cardiac injury. It has been reported that microRNA-24-3p (miR-24-3p) may regulate the Keapl by mRNA degradation, whereas Keapl can suppress the activation of Nrf2. However, the role of miR-24-3p in DOX-related cardiotoxicity remains unclear. The mice receiving DOX were used as cardiac injury model. In this study, an adenoassociated virus 9 system was used to deliver miR-24-3p or miR-scramble to mice hearts. The echocardiographic and hemodynamic analyses were used to evaluate the effects of miR-24-3p on cardiac function under DOX stimulation. ELISA and RT-PCR were used to detect protein or mRNA expressions associated with cardiac injury, inflammation response, apoptosis and oxidative stress. Western Blot were used for quantitative analysis of the roles of miR-24-3p in regulating Nrf2 expression. H9C2 cells used to verify the role of miR-24-3p in vitro. We found that miR-24-3p mRNA was significantly decreased in DOX-treated mice and cardiomyocytes. Overexpression of miR-24-3p blocked cardiac injury caused by DOX injection, as reflected by the reduction in the levels of cardiac troponin I, creatinine kinase isoenzyme MB and the N-terminal pro brain natriuretic peptide. Furthermore, miR-24-3p reduced oxidative stress and cell loss without affecting the inflammation response. As expected, we found that Nrf2 was upregulated by miR-24-3p supplementation, and that the protective efforts of miR-24-3p supplementation were abolished when Nrf2 was silenced. The results from this study suggest that miR-24-3p protects cardiomyocytes against DOX-induced heart injury via activation of the Nrf2 pathway. miR-24-3p supplementation may be a novel strategy to counteract the cardiac side effects of DOX treatment.

Estudo da especificidade da isoenzima MB da creatinaquinase na cirurgia cardíaca com circulação extra-corporal (fases pré, intra e pós operatória).

Estudaram-se em 6 doentes com valvulopatias reumatismais, as variações da actividade enzimática no plasma, durante e apos a cirurgia cardíaca com circulação extra-corporal, para verificar a especificidade da isoenzima MB da creatinaquinase, comparando-a com a da CK. Estudaram-se também as variações da desidrogenase láctica no mesmo período. O protocolo de colheitas escolhido, procurava dissociar as variações enzimáticas correspondentes aos tempos anteriores a miocardiotomia, das relacionadas com a lesão cirúrgica das fibras miocárdicas. Os autores verificaram existir um paralelismo evidente entre as curvas referentes a CK total e a sua isoenzima MB. Esta última elevava-se mais tardiamente, apenas durante os tempos cardíacos da intervenção, atingia o máximo no final desta e voltava mais rapidamente aos valores iniciais. A CK-MB regressava aos valores basais no 3º dia do pós-operatório e a CK-total entre o 5.° e o 7º dia. Os autores concluem que a isoenzima CK-MB é um indicador fiel e pouco sujeito a erros para detecção precoce de sofrimento das fibras musculares cardíacas. Os valores da LDH sofreram variações mais irregulares, atribuíveis a interferência de diversos factores, mas pareceram de interesse na detecção de complicações durante o pós-operatório.

Clinical Efficacy of Subhypothermia in the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy Combined with Myocardial Damage

Objective. To investigate the efficacy of subhypothermia in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE) combined with myocardial damage. Methods. 136 children with HIE and myocardial damage admitted to our hospital from October 2019 to October 2021 were included in the study and were divided into study group and control group of 68 cases each according to the random number table method. The control group was given conventional treatment, and the study group was treated with subhypothermia therapy on top of the control group. Comparing the effects of treatment between the two groups. The serum levels of S-100 β protein, Tau protein, neuron-specific enolase (NSE), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase ( ɑ-HBDH), myoglobin (Myo), cardiac trophic factor-1 (CT-1), cardiac troponin I (cTnI), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), interleukin-1 β (IL-1 β), interleukin-8 (IL-8), and tumor necrosis factor- ɑ (TNF- ɑ) were measured in both groups before and after treatment, respectively. Results. The total effective rate was higher in the study group (88.24%) than in the control group (72.06%) ([Formula: see text]). After treatment, the serum levels of S-100 β protein, Tau protein, NSE, CK, CK-MB, LDH, ɑ-HBDH, Myo, CT-1, cTnI, ROS, IL-1 β, IL-8, and TNF- ɑ were reduced in both groups, and the study group was lower than the control group ([Formula: see text]). The serum levels of SOD and GSH-Px were higher in both groups after treatment than before treatment and were higher in the study group than in the control group ([Formula: see text]). Conclusion. Subhypothermia treatment of children with HIE combined with myocardial injury can further improve the hypoxic-ischemic state; reduce myocardial damage, oxidative stress, and inflammatory response; and has a good overall efficacy.

Prognostic factors in children with acute fulminant myocarditis receiving venoarterial extracorporeal membrane oxygenation.

Pediatric acute fulminant myocarditis (AFM) is a very dangerous disease that may lead to acute heart failure or even sudden death. Previous reports have identified some prognostic factors in adult AFM; however, there is no such research on children with AFM on venoarterial extracorporeal membrane oxygenation (VA-ECMO). This study aimed to find relevant prognostic factors for predicting adverse clinical outcomes. A retrospective analysis was performed in an affiliated university children's hospital with consecutive patients receiving VA-ECMO for AFM from July 2010 to November 2020. These children were classified into a survivor group (n=33) and a non-survivor group (n=8). Patient demographics, clinical events, laboratory findings, and electrocardiographic and echocardiographic parameters were analyzed. Peak serum creatinine (SCr) and peak creatine kinase isoenzyme MB during ECMO had joint predictive value for in-hospital mortality (p=0.011, AUC=0.962). Based on multivariable logistic regression analysis, peak SCr level during ECMO support was an independent predictor of in-hospital mortality (OR=1.035, 95% CI 1.006 to 1.064, p=0.017, AUC=0.936, with optimal cut-off value of 78 μmol/L). Tissue hypoperfusion and consequent end-organ damage ultimately hampered the outcomes. The need for left atrial decompression indicated a sicker patient on ECMO and introduced additional risk for complications. Earlier and more cautious deployment would likely be associated with decreased risk of complications and mortality.

Effect of Virus Inactivation by Heating on Routine Clinical Laboratory Indicators in Serum.

Highly infectious viruses such as SARS-CoV-2, MERS-CoV, and Ebola virus represent a threat to clinical laboratory workers. We aimed to investigate how virus inactivation by heating at 60°C for 1 hour affects routine clinical laboratory indicators. Each collected serum sample was separated into two aliquots, and various indicators were measured in first aliquot after inactivation by heating at 60°C for 1 hour and in the second after room-temperature incubation for 1 hour. Serological test results for 36 indicators remained mostly unaffected by heat inactivation, with a mean estimated bias of < 10%. By contrast, the results for alanine transaminase, pseudocholinesterase, creatine kinase, lactate dehydrogenase, cardiac troponin I, and myoglobin were affected by heat inactivation, with the mean esti-mated bias here being > 20%, which was further increased in the case of the results for alkaline phosphatase, lipase, and creatine kinase isoenzyme MB. Immunological serological measurements showed good agreement according to Kappa consistency checks after heat inactivation of serum. The results for alanine transaminase, pseudocholinesterase, creatine kinase, lactate dehydrogenase, cardiac troponin I, and myoglobin were significantly correlated (r > 0.95) after heat inactivation, and after correction by using a regression equation, the results for the indicators still retained a clinical reference value. Inactivation by heating at 60°C for 1 hour exerts no marked effect on numerous routine biochemical and immunological indicators in serum, but the detection values for certain items are significantly decreased. Our method could serve as reference strategy for routine serological diagnostics in patients with suspected or confirmed infection with highly pathogenic viruses.