Additive Effects of Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker, on Cardioplegic Arrest in Rat Hearts.

PURPOSE: Esaxerenone, a mineralocorticoid receptor blocker, attenuates global ischemia-induced myocardial damage and coronary endothelial dysfunction. This study aimed to determine whether esaxerenone exerted cardioprotective effects against cardioplegic arrest in Wistar rat hearts. METHODS: Isolated male Wistar rat hearts aerobically perfused via the Langendorff method for 20 min were randomly allocated to the Control (n = 6; perfused for an additional 10 min and subjected to no treatment) or Esax (n = 6; perfused with 0.1 µmol/L esaxerenone in perfusate for 10 min before ischemia) groups. Hearts in both groups were perfused with St. Thomas' Hospital No. 2 solution (STH2) for 2 min and subjected to 28 min of global ischemia. The recovery of left ventricular developed pressure (LVDP) and total troponin T leakage were measured after reperfusion. RESULTS: The final recovery of LVDP (expressed as a percentage of pre-ischemic value) in the Control and Esax groups was 50.8 ± 3.5% and 62.1 ± 5.6%, respectively (p <0.05, Esax vs. Control). The total troponin T leakage in the Control and Esax groups was 138.8 ± 18.5 ng/g heart wt and 74.3 ± 18.6 ng/g heart wt, respectively (p <0.05, Esax vs. Control). CONCLUSION: The administration of esaxerenone before cardioplegic arrest enhanced the cardioprotective effect exerted by STH2.

[Study on novel inflammatory indicators in marathon exercise monitoring].

To analyze the changes in lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammatory indices (neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammation index) before and after competitions in amateur marathon runners, and to assess the effects of myocardial injury due to acute exercise and the value of novel inflammatory indices in marathon exercise monitoring. This paper is an analytical study. Amateur athletes recruited by Beijing Hospital to participate in the 2022 Beijing Marathon and the 2023 Tianjin Marathon, and those who underwent health checkups at the Beijing Hospital Medical Checkup Center from January to June 2023 were selected as the study subjects, and 65 amateur marathon runners (41 males and 24 females) and 130 healthy controls (82 males and 48 females) were enrolled in the study according to the inclusion criteria. Peripheral blood was collected one week before, immediately after, and one week after running, and routine blood tests, cardiac enzymes, infarction markers, N-terminal B-type natriuretic peptide precursor, and homocysteine were performed to calculate the values of novel inflammatory indexes. Wilcoxon signed-rank test and Spearman's rank correlation analysis were used to compare the differences in the levels of each index between the amateur marathon population and the health checkup population, and to compare the changes and correlations of each index at the three time points in the amateur marathoners.The results showed that the neutrophil-lymphocyte ratios of the healthy physical examination population and 65 amateur marathoners 1 week before running were 1.73 (1.33, 2.16) and 1.67 (1.21, 2.16), the platelet-lymphocyte ratios were 122.75 (96.69, 155.89) and 120.86 (100.74, 154.63), and the systemic immune inflammation index was 398.62 (274.50, 538.69) and 338.41 (258.62, 485.38), etc.; on 1 week before running, immediately after running and 1 week after running, lactate dehydrogenase of 65 amateur marathon runners was 173.00(159.00, 196.50)U/L,284.00(237.50, 310.50)U/L, 183.00(165.50, 206.50)U/L, creatine kinase was 131.00(94.30, 188.20)U/L,318.00(212.00, 573.15)U/L,139.00(90.55, 202.40)U/L, creatine kinase isoenzyme was 2.50(1.76, 3.43)µg/L,6.24(4.87, 10.30)µg/L,2.73(1.57, 4.40)µg/L.In 65 amateur marathon runners, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammation markers were significantly elevated in the immediate post-run period compared with 1 week before the run, and the differences were statistically significant (Z=-7.009, Z=-6.813, Z=-6.885, Z=-7.009, Z=-7.009, Z=-6.656; P<0.05 for the above indicators).Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammatory index all showed significant positive correlation with the pre-and post-run rates of change of high-sensitivity troponin T (ρ=0.28, P=0.03;ρ=0.31, P=0.01;ρ=0.27, P=0.03); these 3 markers were also significantly and positively correlated with the pre-and post-run rates of change in a collection of myocardial-related markers such as lactate dehydrogenase, creatine kinase, creatine kinase isozymes, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, and homocysteine, respectively(r=0.446, P=0.039; r=0.452, P=0.033; r=0.449, P=0.036).In addition, the platelet-lymphocyte ratio was positively correlated with the pre-and post-run rates of change in creatine kinase and creatine kinase isoenzymes(ρ=0.27, P=0.03;ρ=0.28, P=0.02).In conclusion, acute myocardial injury may be triggered during marathon exercise. Changes in novel inflammatory markers were significantly associated with changes in myocardial enzymes, infarction markers, N-terminal B-type natriuretic peptide precursors, and homocysteine, which may be of value for the prediction of myocardial injury during exercise.

Effect of Single High-Dose Vitamin D3 Supplementation on Post-Ultra Mountain Running Heart Damage and Iron Metabolism Changes: A Double-Blind Randomized Controlled Trial.

Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D3, which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D3 24 h prior to a race (n = 16), while the other group received a placebo (n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run.

Echocardiographic Strain Abnormalities Precede Left Ventricular Hypertrophy Development in Hypertrophic Cardiomyopathy Mutation Carriers.

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen-) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen-. Sixteen Gen+/Phen- (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH-) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (-19.8 ± 0.4 vs. -22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen- subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment.

Association between severity of pulmonary embolism and health-related quality of life.

Background: Health-related quality of life (QoL) impairment is common after pulmonary embolism (PE). Whether the severity of the initial PE has an impact on QoL is unknown. Objectives: To evaluate the association between severity of PE and QoL over time. Methods: We prospectively assessed PE-specific QoL using the Pulmonary Embolism Quality of Life (lower scores indicate better QoL) questionnaire and generic QoL using the Short Form 36 (higher scores indicate better QoL) questionnaire at baseline and 3 and 12 months in older patients with acute PE. We examined whether QoL differed by PE severity based on hemodynamic status, simplified Pulmonary Embolism Severity Index (sPESI), right ventricular function, and high-sensitivity troponin T in mixed-effects models, adjusting for known QoL predictors after PE. Results: Among 546 patients with PE (median age, 74 years), severe vs nonsevere PE based on the sPESI was associated with a worse PE-specific (adjusted mean Pulmonary Embolism Quality of Life score difference of 6.1 [95% CI, 2.4-9.8] at baseline, 7.6 [95% CI, 4.0-11.3] at 3 months, and 6.7 [95% CI, 2.9-10.4] at 12 months) and physical generic QoL (adjusted mean Short Form 36 Physical Component Summary score difference of -3.8 [95% CI, -5.5 to -2.1] at baseline, -4.8 [95% CI, -6.4 to -3.1] at 3 months, and -4.1 [95% CI, -5.8 to -2.3] at 12 months). Elevated troponin levels were also associated with lower PE-specific QoL at 3 months and lower physical generic QoL at 3 and 12 months. QoL did not differ by hemodynamic status or right ventricular function. Conclusion: Severe PE based on the sPESI was consistently associated with worse PE-specific and physical generic QoL over time as compared to nonsevere PE.

Cardiac autonomic regulation following a 246-km mountain ultra-marathon: An observational study.

Physical exercise requires integrated autonomic and cardiovascular adjustments to maintain homeostasis. We aimed to observe acute posture-related changes in blood pressure, and apply a portable noninvasive monitor to measure the heart index for detecting arrhythmia among elite participants of a 246-km mountain ultra-marathon. Nine experienced ultra-marathoners (8 males and 1 female) participating in the Run Across Taiwan Ultra-marathon in 2018 were enrolled. The runners' Heart Spectrum Blood Pressure Monitor measurements were obtained in the standing and supine positions before and immediately after the race. Their high-sensitivity troponin T and N-terminal proB-type natriuretic peptide levels were analyzed 1 week before and immediately after the event. Heart rate was differed significantly in the immediate postrace assessment compared to the prerace assessment, in both the standing (P = .011; d = 1.19) and supine positions (P = .008; d = 1.35). Postural hypotension occurred in 4 (44.4%) individuals immediately postrace. In 3 out of 9 (33.3%) recruited finishers, the occurrence of premature ventricular complex signals in the standing position was detected; premature ventricular complex signal effect was observed in the supine position postrace in only 1 participant (11.1%). Premature ventricular complex signal was positively correlated with running speed (P = .037). Of the 6 individuals who completed the biochemical tests postrace, 2 (33.3%) had high-sensitivity troponin T and 6 (100%) had N-terminal proB-type natriuretic peptide values above the reference interval. A statistically significant increase was observed in both the high-sensitivity troponin T (P = .028; d = 1.97), and N-terminal proB-type natriuretic peptide (P = .028; d = 2.91) levels postrace compared to prerace. In conclusion, significant alterations in blood pressure and heart rate were observed in the standing position, and postexercise (postural) hypotension occurred among ultra-marathoners. The incidence of premature ventricular complexes was higher after the race than before.

[False positive on macrotroponin]. / Faux positif lié à une macrotroponinémie élevée.

The determination of I and T subunits of cardiac troponin isoforms are the biochemical gold standard for the detection of myocardial distress. The advent of so-called highly sensitive measurements has optimized the diagnosis of acute coronary syndromes at the cost of making the diagnostic approach more complex and increasing sensitivity to analytical interference. This article presents a case of macrotroponinemia, characterized by circulating IgG-troponin T immunocomplexes, in order to raise prescribers' awareness of the critical interpretation of high and persistent cardiac troponin values.

Le dosage des sous-unités I et T des isoformes cardiaques de troponines est le gold-standard biochimique de la détection de la souffrance myocardique. L'avènement des mesures dites hautement sensibles a optimisé le diagnostic des syndromes coronariens aigus au prix d'une complexification de la démarche diagnostique et d'une sensibilité accrue aux interférences analytiques. Cet article présente un cas de macrotroponinémie, caractérisé par des immunocomplexes IgG-troponine T circulants, afin de sensibiliser les prescripteurs à l'interprétation critique des valeurs élevées et persistantes de troponines cardiaques (cTn).

The difference in core-surface temperature indicates the prognosis of heart failure patients.

Aim: To evaluate the difference between core temperature and surface temperature (ΔT) as an index for the prognosis of heart failure (HF). Patients & methods: Core temperature and surface temperature were measured in 253 patients with HF. The association of ΔT with prognostic indicators of HF was analyzed. Results: Patients with ΔT ≥2°C were more likely to have lower left ventricular ejection fraction and lower estimated glomerular filtration rate, higher levels of troponin T, brain natriuretic peptide and procalcitonin, and high blood urea nitrogen/creatinine ratio. The risk of death increased by 32% for a 1°C increase in ΔT and was 4.36-times higher in the ΔT ≥2°C group than in the ΔT <2°C group. Conclusion: ΔT may be used to predict the prognosis of patients with HF.

[Box: see text].

High-Sensitivity Cardiac Troponin T and Frailty Predict Short-Term Mortality in Patients ≥75 Years Undergoing Emergency Abdominal Surgery: A Prospective Observational Study.

BACKGROUND: An elevated cardiac troponin concentration is a prognostic factor for perioperative cardiac morbidity and mortality. In elderly patients undergoing emergency abdominal surgery, frailty is a recognized risk factor, but little is known about the prognostic value of cardiac troponin in these vulnerable patients. Therefore, we investigated the prognostic significance of elevated high-sensitivity cardiac troponin T (hs-cTnT) concentration and frailty in a cohort of elderly patients undergoing emergency abdominal surgery. METHODS: We included consecutive patients ≥75 years of age who presented for emergency abdominal surgery, defined as abdominal pathology requiring surgery within 72 hours, in a university hospital in Norway. Patients who underwent vascular procedures or palliative surgery for inoperable malignancies were excluded. Preoperatively, frailty was assessed using the Clinical Frailty Scale (CFS), and blood samples were measured for hs-cTnT. We evaluated the predictive power of CFS and hs-cTnT concentrations using receiver operating characteristic (ROC) curves and Cox proportional hazard regression with 30-day mortality as the primary outcome. Secondary outcomes included (1) a composite of 30-day all-cause mortality and major adverse cardiac event (MACE), defined as myocardial infarction, nonfatal cardiac arrest, or coronary revascularization; and (2) 90-day mortality. RESULTS: Of the 210 screened and 156 eligible patients, blood samples were available in 146, who were included. Troponin concentration exceeded the 99th percentile upper reference limit (URL) in 83% and 89% of the patients pre- and postoperatively. Of the participants, 53% were classified as vulnerable or frail (CFS ≥4). The 30-day mortality rate was 12% (18 of 146). Preoperatively, a threshold of hs-cTnT ≥34 ng/L independently predicted 30-day mortality (hazard ratio [HR] 3.14, 95% confidence interval [CI], 1.13-9.45), and the composite outcome of 30-day mortality and MACE (HR 2.58, 95% CI, 1.07-6.49). In this model, frailty (continuous CFS score) also independently predicted 30-day mortality (HR 1.42, 95% CI, 1.01-2.00) and 30-day mortality or MACE (HR 1.37, 95% CI, 1.02-1.84). The combination of troponin and frailty, 0.14 × hs-cTnT +4.0 × CFS, yielded apparent superior predictive power (area under the receiver operating characteristics curve [AUC] 0.79, 95% CI, 0.68-0.88), compared to troponin concentration (AUC 0.69, 95% CI, 0.55-0.83) or frailty (AUC 0.69, 95% CI, 0.57-0.82) alone. CONCLUSIONS: After emergency abdominal surgery in elderly patients, increased preoperative troponin concentration and frailty were independent predictors of 30-day mortality. The combination of increased troponin concentration and frailty seemed to provide better prognostic information than troponin or frailty alone. These results must be validated in an independent sample.

Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T.

AIMS: Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. METHODS AND RESULTS: Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase > 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, >100, >200, or >300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89), and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82), and 54% (95% CI 25-81). In CKD patients with a 2 h hs-cTnT delta of ≥10, >20, or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96), and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86), and 75% (95% CI 58-88). CONCLUSION: Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

Nitric Oxide/Glucose Transporter Type 4 Pathway Mediates Cardioprotection against Ischemia/Reperfusion Injury under Hyperglycemic and Diabetic Conditions in Rats.

INTRODUCTION: The comorbidities of ischemic heart disease (IHD) and diabetes mellitus (DM) compromise the protection of the diabetic heart from ischemia/reperfusion (I/R) injury. We hypothesized that manipulation of reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways might protect the diabetic heart, and intervention of these pathways could be a new avenue for potentially protecting the diabetic heart. METHODS: All hearts were subjected to 30-min ischemia and 30-min reperfusion. During reperfusion, hearts were exposed to molecules proven to protect the heart from I/R injury. The hemodynamic data were collected using suitable software. The infarct size, troponin T levels, and protein levels in hearts were evaluated. RESULTS: Both cyclosporine-A and nitric oxide donor (SNAP) infusion at reperfusion protected 4-week diabetic hearts from I/R injury. However, 6-week diabetic hearts were protected only by SNAP, but not cyclosporin-A. These treatments significantly (p < 0.05) improved cardiac hemodynamics and decreased infarct size. CONCLUSIONS: The administration of SNAP to diabetic hearts protected both 4- and 6-week diabetic hearts; however, cyclosporine-A protected only the 4-week diabetic hearts. The eNOS/GLUT-4 pathway executed the SNAP-mediated cardioprotection.

Risk factors and outcomes associated with systolic dysfunction following traumatic brain injury.

Systolic dysfunction has been observed following isolated moderate-severe traumatic brain injury (Ims-TBI). However, early risk factors for the development of systolic dysfunction after Ims-TBI and their impact on the prognosis of patients with Ims-TBI have not been thoroughly investigated. A prospective observational study among patients aged 16 to 65 years without cardiac comorbidities who sustained Ims-TBI (Glasgow Coma Scale [GCS] score ≤12) was conducted. Systolic dysfunction was defined as left ventricular ejection fraction <50% or apparent regional wall motion abnormality assessed by transthoracic echocardiography within 24 hours after admission. The primary endpoint was the incidence of systolic dysfunction after Ims-TBI. The secondary endpoint was survival on discharge. Clinical data and outcomes were assessed within 24 hours after admission or during hospitalization. About 23 of 123 patients (18.7%) developed systolic dysfunction after Ims-TBI. Higher admission heart rate (odds ratios [ORs]: 1.05, 95% confidence interval [CI]: 1.02-1.08; P = .002), lower admission GCS score (OR: 0.77, 95% CI: 0.61-0.96; P = .022), and higher admission serum high-sensitivity cardiac troponin T (Hs-cTnT) (OR: 1.14, 95% CI: 1.06-1.22; P < .001) were independently associated with systolic dysfunction among patients with Ims-TBI. A combination of heart rate, GCS score, and serum Hs-cTnT level on admission improved the predictive performance for systolic dysfunction (area under curve = 0.85). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality of patients with systolic dysfunction was higher than that of patients with normal systolic function (P < .05). Lower GCS (OR: 0.66, 95% CI: 0.45-0.82; P = .001), lower admission oxygen saturation (OR: 0.82, 95% CI: 0.69-0.98; P = .025), and the development of systolic dysfunction (OR: 4.85, 95% CI: 1.36-17.22; P = .015) were independent risk factors for in-hospital mortality in patients with Ims-TBI. Heart rate, GCS, and serum Hs-cTnT level on admission were independent early risk factors for systolic dysfunction in patients with Ims-TBI. The combination of these 3 parameters can better predict the occurrence of systolic dysfunction.

High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT.

BACKGROUND: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets. METHODS: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories. RESULTS: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; Pinteraction=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively. CONCLUSIONS: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.

TNNT1 accelerates migration, invasion and EMT progression in lung cancer cells.

BACKGROUND: Clinically, most patients with lung cancer (LC) die from tumor spread and metastasis. Specific metastasis-related molecules can provide reference for clinical prediction of efficacy, evaluation of prognosis, and search for the best treatment plan. Troponin T1 (TNNT1) is highly expressed in various cancer tissues, which affects malignant behavior of tumor cells and is related to patients' survival and prognosis. However, the role and molecular mechanism of TNNT1 in LC invasion and metastasis have not yet been investigated. METHODS: Gene expression profiling interactive analysis (GEPIA) online analysis was used to analyze TNNT1 expression in LC tissues. Quantitative real-time-polymerase chain reaction (qRT-PCR) or western blot were performed to measure TNNT1 or epithelial-to-mesenchymal transition (EMT)-related and Wnt/ß-catenin pathway-related protein expression in LC cells. After TNNT1 knockdown, cell scratch healing and transwell assays were introduced to assess cell migration and invasion, respectively. RESULTS: TNNT1 expression in LC tissues and cells was increased. TNNT1 knockdown notably impaired LC cell migration, invasion and EMT. TNNT1 knockdown inhibited Wnt/ß-catenin pathway of LC cells. Lithium chloride (LiCl) addition partially restored the inhibition of TNNT1 knockdown on migration, invasion, EMT and Wnt/ß-catenin of LC cells. CONCLUSION: TNNT1 knockdown attenuated LC migration, invasion and EMT, possibly through Wnt/ß-catenin signaling.

Establishment of a human induced pluripotent stem cell line from a patient with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the main causes of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation worldwide. Mutations in dozens of cardiac genes have been connected to the development of DCM including the Troponin T2 gene (TNNT2). Here, we generated a human induced pluripotent stem cells (hiPSCs) from a DCM patient with a familial history that carries a missense mutation in TNNT2. The hiPSCs show typical morphology of pluripotent stem cells, expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers.

Troponin T1 in tumorigenesis and immune modulation: Insights into multiple cancers and kidney renal clear cell carcinoma.

Troponin T1 (TNNT1) plays a crucial role in muscle contraction but its role in cancer, particularly in kidney renal clear cell carcinoma (KIRC), is not well-understood. This study explores the expression, clinical significance and biological functions of TNNT1 in various cancers, with an emphasis on its involvement in KIRC. We analysed TNNT1 expression in cancers using databases like TCGA and GTEx, assessing its prognostic value, mutation patterns, methylation status and functional implications. The study also examined TNNT1's effect on the tumour microenvironment and drug sensitivity in KIRC, complemented by in vitro TNNT1 knockdown experiments in KIRC cells. TNNT1 is overexpressed in several cancers and linked to adverse outcomes, showing frequent upregulation mutations and abnormal methylation. Functionally, TNNT1 connects to muscle and cancer pathways, affects immune infiltration and drug responses, and its overexpression in KIRC is associated with advanced disease and reduced survival. Knocking down TNNT1 curbed KIRC cell growth. TNNT1's aberrant expression plays a significant role in tumorigenesis and immune modulation, highlighting its value as a prognostic biomarker and a potential therapeutic target in KIRC and other cancers. Further studies are essential to understand TNNT1's oncogenic mechanisms in KIRC.

Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest.

Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.

Cardiovascular medications, high-sensitivity cardiac troponin T concentrations, and long-term outcome in non-ST segment elevation acute coronary syndrome.

AIMS: Cardiac troponin plays an essential role in the management of non-ST segment elevation acute coronary syndrome (NSTE-ACS). However, it is not clear whether troponin concentrations provide guidance regarding the initiation of prognostically beneficial cardiovascular medications [i.e. betablockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and statins] in NSTE-ACS. METHODS AND RESULTS: Registry-based study investigating three NSTE-ACS cohorts (n = 43 075, 40 162, and 46 698) with elevated high-sensitivity cardiac troponin concentrations >14 ng/L. Cox proportional regression models with the addition of interaction terms were used to analyse the interrelations of high-sensitivity cardiac troponin T (hs-cTnT) concentrations, new initiated medications with the respective three drug classes, and long-term risk of all-cause mortality and major adverse events (MAE). Betablockers were associated with risk reductions of 8 and 5% regarding all-cause mortality and MAE, respectively. There was no evidence of an interaction with hs-cTnT concentrations. RAAS inhibitors were associated with 13 and 8% risk reductions, respectively, with a weak interaction between hs-cTnT and MAE (Pinteraction = 0.016). However, no increasing prognostic benefit was noted at hs-cTnT concentrations >100 ng/L. Statins were associated with 38 and 32% risk reductions, respectively, with prognostic benefit across the entire range of hs-cTnT concentrations, and with a weak interaction regarding MAE (Pinteraction = 0.011). CONCLUSION: Cardiovascular medications provide different prognostic benefit in patients with NSTE-ACS with elevated hs-cTnT, and there was some evidence of greater treatment effects regarding MAE along with higher hs-cTnT concentrations. However, hs-cTnT appears only to have limited value overall for customizing such treatments.