MAPK/c-Jun/TNNT1 pathway regulates cytoskeletal remodeling and promotes tumor invasion and metastasis in HNSCC.

The bidirectional interaction between inflammation and thrombus formation plays an important role in myocardial infarction (MI) with IL (interleukin)-6 as a central mediator. If anti-inflammatory therapy modulates coagulation factors, and platelet activation in patients with MI is not clear. We have shown that tocilizumab, a monoclonal antibody targeting IL-6R (IL-6 receptor), improves myocardial salvage index in patients with ST-elevation MI. Herein, we measured levels of soluble markers of platelet activation (P-selectin, sCD40L [soluble CD40 ligand]) and coagulation (TF [tissue factor], TFPI [TF pathway inhibitor], PAI [plasminogen activator inhibitor]-1, and D-dimer) in 136 patients with ST-segment-elevation MI (70 tocilizumab and 66 placebo). Platelet-poor EDTA plasma samples were obtained at admission and after 24 and 168 hours. Temporal changes were related to TnT (troponin T), as well as infarct size and myocardial salvage index, assessed by cardiac magnetic resonance imaging. Our major findings were given as follows: (1) patients had higher sCD40L, P-selectin, TFPI, and D-dimer than 28 healthy controls, and these increased during 1-week follow-up, while TFPI decreased; (2) tocilizumab attenuated P-selectin in patients with short symptom duration at 24 hours in particular in those with high C-reactive protein, and this change correlated positively with indices of myocardial damage; (3) tocilizumab augmented TF at 168 hours, and this change correlated positively with infarct size and negatively with myocardial salvage index; (4) change in D-dimer at 168 hours correlated positively with infarct size and negatively with myocardial salvage index in particular in those with long symptom durations or treated with placebo; tocilizumab attenuated these changes; and (5) the use of heparin attenuated sCD40L levels and increased TFPI levels in admission samples and TF levels after 168 hours. Our findings support attenuation of platelet activation/coagulation by tocilizumab in patients with ST-segment-elevation MI. The marked rise in TF could be a hereto unrecognized side effects of tocilizumab, which need further investigation.

Thin filament interaction and Ca2+-desensitization effect of the C-terminal end peptide of cardiac troponin T and loss of function in hypertrophic cardiomyopathy mutants.

BackgroundMyocardial injury after non-cardiac surgery (MINS) contributes to mortality after major open abdominal surgery. While intraoperative hypotension (IOH) is a proposed cause, its impact—defined using comprehensive thresholds—in this specific high-risk cohort remains underexplored. This study aimed to determine the association between the severity and duration of IOH and MINS.MethodsWe assessed patients undergoing open abdominal surgery with invasive blood pressure monitoring in a single-center retrospective cohort study conducted between June 2016 and July 2019. The primary exposure, IOH, was defined using three absolute and three relative thresholds of mean arterial pressure (MAP), according to established literature and clinical consensus. The primary outcome was MINS (serum Troponin T (TnT) ≥ 0.03 ng/mL within 30 days after surgery). A multivariable logistic regression analysis was applied to model the exposure–outcome relationship, adjusting for potential clinical confounders.ResultsOf the 8,281 patients screened, 1,461 met the inclusion criteria. MINS occurred in 175 patients (12.0%). MAP below three absolute thresholds (≤65, ≤60, and ≤55 mmHg) and three thresholds relative to the preinduction MAP (decreases of >30, >40, and >50% from baseline) were independently associated with MINS. For MAP ≤60 mmHg, the odds of MINS increased with longer durations of hypotension, rising from 1.54 (95% CI 0.98–2.44) for 1–5 min to 3.81 (95% CI 2.20–6.61) for ≥21 min. At the longest duration, lower MAP thresholds were associated with higher risk (OR 3.66 for ≤65 mmHg; 3.81 for ≤60 mmHg; and 8.42 for ≤55 mmHg). Similar associations were observed for relative MAP reductions.ConclusionIn major open abdominal surgery patients, IOH, either based on absolute and relative thresholds, is independently and cumulatively associated with MINS. Associations based on absolute MAP thresholds appeared more consistent, whereas those based on relative reductions showed greater variability.

Individual pre-slaughter muscle proteolysis levels correlated with postmortem taste-related amino acid concentrations in broiler chickens.

BackgroundNeonates born with hypoplastic left heart syndrome (HLHS) or complex (HLHC), who undergo stage I palliation with Norwood operation or Damus-Kaye-Stansel (DKS), still carry substantial mortality and morbidity even in the modern era of cardiac surgery. Mortality varies from 10% up to 40% in some Institutions, remaining still one of the highest in pediatric cardiac surgery. In order to reduce mortality and morbidity, we have developed a strategy of selective cerebro-myocardial perfusion (sCMP), allowing to perform the entire operation on the beating heart. The aim of the presents report is to describe our results with such an innovative approach.MethodsBetween December 2016 to December 2024, 12 consecutive patients underwent Norwood-Brawn/double-barrel DKS stage I palliation for single ventricle (SV) palliation associated with ascending aorta and severe arch hypoplasia. All patients were managed with a 3.5 mm modified Blalock-Taussig (mBT) shunt, except one 5-month infant who had a 4 mm shunt. The operation was performed under mild hypothermia with selective constant coronary and cerebral perfusion provided by 2 separate pump rotors.ResultsThere were 6 male and 6 female patients, with a median age of 4.5 days [interquartile range (IQR), 2.75–5.25 days] and median body weight of 3.2 kg (IQR, 3.075–3.55 kg). Median cardiopulmonary bypass (CPB) time was 200 min (166–306 min), the median time of myocardial perfusion 80 min (67.5–90 min), the median time of cerebral perfusion time was 160 min (150–176.25 min) and the median time of splanchnic ischemia during cerebro-myocardial perfusion was 47 (40.75–53.5 min). In the series only 2 patients required veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) for failure to wean from bypass. The mean peak troponin T (TnT) was 5,973 (IQR, 1,775.5–8,971) ng/L, while the mean peak lactate level was 8.9 (5.55–11.95) mmol/L. Acute kidney injury, requiring a transient period of peritoneal dialysis was observed in 9 of 12 (75%) patients, while no patients developed liver dysfunction. Postoperative death occurred in 2 patients affected by one of the most severe forms of HLHS (mitro-aortic atresia) due to cardiac dysfunction and failure to wean from VA ECMO support. There was one interstage mortality (between stage I and II) due to progressive heart failure and sepsis. During a median follow-up of 52 months (13–73 months) all late survival were in good clinical conditions without signs of cardiac dysfunction and trivial systemic valve regurgitation. Nine patients completed II stage and six of them stage III palliation of the univentricular heart.ConclusionsThe present experience suggests that a strategy of cerebro-myocardial perfusion is safe, versatile, and feasible in high-risk neonates with HLHC. Encouraging outcomes were noted in terms of cardiac and neurological function, with limited end-organ morbidity.

Toward practical screening of mortality risk: Insights from interpretable machine learning in NHANES☆

Integrating transcriptomics and network pharmacology to investigate YangxinDingji Capsule alleviates myocardial injury in tachyarrhythmia rat.

Cardiac troponin serves as a biomarker for diagnosing myocardial contusion following blunt chest trauma and for differentiating between types of myocardial infarction. However, its interpretation in polytrauma remains challenging due to overlapping pathophysiological mechanisms. This study aims to improve troponin-based cardiac risk stratification to more accurately identify high-risk patients and enhance prognostic assessment. This prospectively performed study included polytraumatized patients (ISS ≥ 16) admitted to a German Level 1 trauma center between January 2024 and July 2025. For each patient, six blood samples collected over ten days were analyzed for Troponin T (TnT) and NT-proBNP; and two transthoracic echocardiograms (24h and 48h) and ECGs were evaluated by a cardiologist. Data were correlated with clinical records, trauma-dependent and -independent cardiac risk factors, including the cardiovascular risk score (SCORE2). Seventy-seven patients were included (mean age 52years; 73% male; mean ISS 29). TnT was elevated in 44% at admission and in 73% after 24h. 13% of the patients were diagnosed with a cardiac contusion. TnT elevation was associated with age ≥ 40years, higher SCORE2, thoracic injuries, ISS ≥ 25, preclinical arrhythmias, catecholamine therapy, and surgery at admission. Two distinct TnT patterns were found:Group 1 (44%)-elevation already at admission, mirrored the overall risk profile but showed more persistent elevation in patients ≥ 60years, with very high SCORE2 or catecholamine therapy and was especially linked to sternal fractures.Group 2 (26%)-delayed TnT rise after 24h, associated with thoracic trauma, ISS ≥ 25, surgery and catecholamine therapy. Complications, including new-onset arrhythmias and higher mortality, occurred in both groups. Cardiac involvement in polytrauma is multifactorial and often underrecognized. TnT elevation was associated with higher age, high SCORE2, severe injury, thoracic trauma, arrhythmias, and resuscitation, with a distinct subgroup showing delayed elevation after 24h. This delayed phenotype is clinically relevant, as most of these patients had thoracic trauma and underwent early surgery, aligning with recommendations for perioperative screening for myocardial infarction. Our findings emphasize routine peri-traumatic and peri-operative troponin measurement and highlight the value of TTE and continuous ECG for detecting evolving cardiac dysfunction. Systematic follow-up is needed to assess long-term outcomes and refine cardiac risk stratification in this vulnerable population.

To investigate the alterations in myocardial injury markers following balloon dilatation combined with thrombectomy in patients with massive pulmonary embolism (MPE). A retrospective study was conducted in 90 patients diagnosed with MPE. Clinical efficacy, Miller scores, pulmonary artery pressure (PAP), pulmonary artery diameter (PAD), and levels of myocardial injury markers were evaluated and compared between the combined treatment group (balloon dilatation plus thrombectomy) and the basic treatment group (basic therapy alone). Compared to the basic treatment group, the combined treatment group exhibited significantly improved clinical efficacy, including higher rates of complete response, marked response, and overall response. Hemodynamic and cardiac function indices were significantly improved, as evidenced by lower post-treatment Miller score, PAP, PAD, and right ventricular/left ventricular (RV/LV) ratios. Myocardial injury and inflammation-related indicators, including myoglobin (MYO), troponin T (TnT), creatine kinase (CK), and fibrinogen (FIB) were significantly reduced at specific time points in the combined treatment group. Furthermore, significant correlations were identified between injury markers and arterial blood gas indices: CK at 24 hours was inversely correlated with arterial partial pressure of carbon dioxide (PaCO2), and TnT at 72 hours was negatively associated with arterial partial pressure of oxygen (PaO2). Balloon dilation combined with thrombectomy for the treatment of MPE can significantly reduce myocardial injury and inflammation-related indicators, thereby markedly improving clinical outcome.

ABSTRACTPatients diagnosed with intermediate high‐risk pulmonary embolism (IHRPE) are at significant risk for clinical deterioration during hospitalization; however, clinical tools to identify which patients will worsen are imprecise. We designed a proof‐of‐concept, single‐center prospective study to assess IHRPE patients (using 2019 ESC criteria), measuring blood concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), troponin T (TnT), uric acid, and plasma lactate serially during the first 72 h to better understand their kinetics and associations with in‐hospital adverse clinical events. Twenty subjects (mean age 62.0 ± 12.6 years) diagnosed by computed tomography angiogram were enrolled. Central pulmonary embolism was seen in 18/20, and lower extremity deep vein thrombosis in 14/20. On presentation, the mean Bova and PESI scores were 5 ± 0.7 and 105 ± 25.2, respectively. At baseline, TnT was elevated in 20/20, NT‐proBNP in 18/20, uric acid in 10/20, and lactate in 8/20 subjects. Clinical outcomes included ICU admission in 7/20, clinical deterioration in 10/20, and death in 2/20. Clinical deterioration was associated with persistent elevations of TnT, NT‐proBNP, uric acid and lactate (all p < 0.05). The NT‐proBNP time from baseline to peak concentration was highly associated with clinical deterioration (ROC AUC = 0.82 [95% CI: 0.62–0.97, p < 0.01, RR = 2.8 at 24 h). The baseline PESI score ROC AUC for clinical deterioration was 0.75 (95% CI: 0.515–0.952, p = NS). Persistently elevated biomarkers show an association with in‐hospital adverse clinical events in IHRPE and warrant further study to assist clinical management.

This study aims to characterize the clinical and genetic features of a sporadic case of dilated cardiomyopathy (DCM) associated with a TNNT2 variant and to review the variant spectrum of the TNNT2 gene in the Chinese DCM population. A 41-year-old male proband diagnosed with DCM underwent comprehensive clinical evaluation. Whole-exome sequencing (WES) was performed on the proband to identify potential causative variants. Subsequently, Sanger sequencing was used to specifically validate the candidate TNNT2 variant in the proband and all available family members. Bioinformatic tools were employed to predict the pathogenicity of the identified variant, which was interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines. A literature review of TNNT2 variants in Chinese DCM patients was conducted. Clinical assessment revealed left ventricular dilation and systolic dysfunction in the proband. Genetic analysis identified a heterozygous missense variant in the TNNT2 gene (c.311G > A, p.Arg104His). Bioinformatic predictions consistently supported its deleterious effect and high conservation. The variant was not found in the available family members. Considering the maternal sudden death history, it is likely to be de novo or maternally inherited. Based on ACMG guidelines, the variant was classified as "Likely Pathogenic". The literature review summarized 14 distinct TNNT2 variants from 20 reported Chinese DCM cases. This study provides a detailed clinical characterization of the TNNT2 c.311G > A (p.Arg104His) variant in a Chinese patient with sporadic DCM, contributing to the understanding of its phenotypic spectrum. The review provides an overview of the TNNT2 variant spectrum in the Chinese DCM population.

ABSTRACTThis study investigated the effects of postmortem aging on the nutritional quality and physicochemical properties of myofibrillar proteins (MFP) in Bactrian camel meat. In this study, hindlimb meat from five Bactrian camels was aged at 4°C and sampled on D0, D1, D3, D5, and D7. Samples were analyzed for proximate composition, amino acid profiles, and the functional and structural properties of MFPs. During aging, the moisture content decreased from 75.86% (D0) to 73.60% (D3) before partially recovering to 74.54% (D7), while protein (≈21.7%), crude fat (≈1.1%), and ash (≈0.86%) remained stable. Total amino acids (TAA) and essential amino acids (EAA) increased significantly, with TAA rising from 20.32 to 22.53 g/100 g and EAA from 9.17 to 9.92 g/100 g (P < 0.05). The EAA/TAA ratio consistently exceeded FAO/WHO recommendations, with lysine showing the highest amino acid score (≈1.6 times the reference value). MFP solubility increased from 25.66% to 76.21%, accompanied by improved emulsifying activity, but gel water‐holding capacity and foaming stability declined. SDS‐PAGE revealed a 30 kDa troponin‐T (TnT) degradation product from D3, while Fourier transform infrared (FTIR) indicated a structural shift from α‐helices (18.21% to 11.56%) to random coils (+5.64%). These results suggest that 3–5 days of aging may optimize both nutritional value and functional properties, providing a practical reference for camel meat processing. The findings are specific to the hindlimb muscle, and further research on different muscles is warranted.

Generation of an induced pluripotent stem cell line (HPCHi002-A) derived from a dilated cardiomyopathy patient harboring heterozygous mutations c.644G > T (p.Arg215Leu) in the TNNT2 gene.

The p.Asn271Ile Variant in the TNNT2 Gene Is Associated With Low-Risk Late-Onset Hypertrophic Cardiomyopathy.

Concomitant cryoablation is routinely performed in patients with atrial fibrillation who undergo minimally invasive atrioventricular (AV) valve surgery. While biomarker thresholds for postoperative myocardial infarction (pMI) are established in coronary artery bypass surgery, no clear thresholds exist after concomitant cryoablation in endoscopic valve surgery. This study aimed to analyze the perioperative cardiac biomarker release patterns in this patient cohort and to evaluate the applicability of SCAI-defined pMI thresholds.We retrospectively analyzed patients who underwent endoscopic AV valve surgery from 2018 to 2024, comparing those with cryoablation (n = 165; mean age: 66.5 ± 9.5 years) to those without (n = 513; mean age: 62.4 ± 12.0 years). Perioperative creatine kinase-myocardial band (CK-MB) and troponin T (TnT) levels were measured before surgery, at 1 and 4 hours after surgery, and on postoperative day 1 (1POD). In-hospital outcomes were also assessed.Cryoablation significantly increased CK-MB (6.4 × ULN vs. 2.4 × ULN, p < 0.001) and TnT (257 × ULN vs. 80 × ULN, p < 0.001). Compared with SCAI pMI criteria (CK-MB > 10 × ULN; TnT > 70 × ULN), CK-MB remained below the threshold, while TnT exceeded it in most cases (p < 0.05). Despite these elevations, clinical pMI was rare (two cases vs. three cases). In-hospital mortality did not differ significantly between the groups (1.2% vs. 1.6%; p = 1.000).Cryoablation during minimally invasive AV valve surgery markedly increases postoperative cardiac biomarkers without higher clinical pMI rates. Procedure-specific biomarker thresholds and validation of SCAI criteria are essential for accurate diagnosis and patient management.

The contraction-relaxation balance of trabecular meshwork (TM) cells is a critical physiological mechanism regulating aqueous humor outflow resistance. Both hypercontractility and impaired relaxation of TM cells can obstruct aqueous humor outflow. Such pathological changes not only directly compromise outflow function but may also reduce the clinical efficacy of ocular hypotensive therapies. However, the molecular regulatory mechanisms underlying TM cell contractility remain incompletely understood. Based on single-cell RNA sequencing data previously generated by our group, our analyses revealed abnormal expression patterns of tropomyosin family members (TPMs) in major TM cell subpopulations in primates with primary open-angle glaucoma (POAG). This study investigated the effects of TPM2 in TM cells on contractile-related molecular expression and biomechanical properties. The results showed that modulating TPM2 expression levels significantly affected the expression of Actin Alpha Cardiac Muscle 1 (ACTC1), Troponin T2, Cardiac Type (TNNT2), alpha-smooth muscle actin (α-SMA), and F-actin in human TM cells (HTMCs), and simultaneously altered the cellular elastic modulus. Thus, TPM2 may regulate aqueous humor outflow by modulating TM cell contractility, altering cytoskeletal architecture, and inducing changes in biomechanical properties.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-24993-7.

BackgroundHeart failure (HF) is a major public health concern in China, but there is a lack of epidemiological data on the prevalence of early-stage HF in the elderly.ObjectivesThis study aimed to evaluate the prevalence of different stages of HF in individuals aged ≥ 60 years in a community-based survey.MethodsThis cross-sectional study enrolled 7,640 participants from a community. Basic demographic information, NT-proBNP, troponin T (TnT) levels, and echocardiographic data were collected. Participants were classified into four stages: Healthy, Stage A, Stage B, and Stage C. Prevalence and associated risk factors were analyzed.ResultsThe mean age was 70.2 years, with 54.5% being female. The prevalence of Stage A and B was 44.0% and 27.8%, respectively. In Stage A, hypertension was the most common risk factor (80.89%), followed by diabetes (29.75%) and obesity (18.08%). In Stage B and C, 97.2% and 88.2% had an ejection fraction ≥ 50%. The prevalence of Stage B increased with age (P < 0.001), and women had higher prevalence of Stage B compared to men (29.69% vs. 25.65%, P < 0.001). Female gender (OR 1.352, P < 0.001), older age (OR 1.096, P < 0.001), atrial fibrillation/flutter (OR 2.853, P < 0.001), and coronary artery disease (OR 1.473, P < 0.001) were identified as significant risk factors for Stage B.ConclusionsThis survey revealed a high prevalence of Stage A and B HF in the elderly, with most Stage B individuals having an ejection fraction ≥ 50%, emphasizing the need for targeted prevention and management strategies for at-risk groups.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12877-025-06631-z.

Comparative predictive value of troponin I and troponin T for in-hospital ischemic and bleeding events in acute coronary syndrome

Early blood-derived predictors of final infarct size in patients with anterior STEMI and primary PCI