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Ventricular tachycardia (VT), which could lead to sudden cardiac death, occurs frequently in patients with myocardial infarction. Computational modeling has emerged as a powerful platform for the non-invasive investigation of lethal heart rhythm disorders in post-infarction patients and for guiding patient VT ablation. However, it remains unclear how VT dynamics and predicted ablation targets are influenced by inter-patient variability in action potential duration (APD) and conduction velocity (CV). The goal of this study was to systematically assess the effect of changes in the electrophysiological parameters on the induced VTs and predicted ablation targets in personalized models of post-infarction hearts. Simulations were conducted in 5 patient-specific left ventricular models reconstructed from late gadolinium-enhanced magnetic resonance imaging scans. We comprehensively characterized all possible pre-ablation and post-ablation VTs in simulations conducted with either an "average human VT"-based electrophysiological representation (i.e., EP) or with ±10% APD or CV (i.e., EP); additional simulations were also executed in some models for an extended range of these parameters. The results showed that: (1) a subset of reentries (76.2-100%, depending on EP parameter set) conducted with ±10% APD/CV was observed in approximately the same locations as reentries observed in EP cases; (2) emergent VTs could be induced sometimes after ablation in EP models, and these emergent VTs often corresponded to the pre-ablation reentries in simulations with EP parameter sets. These findings demonstrate that the VT ablation target uncertainty in patient-specific ventricular models with an average representation of VT-remodeled electrophysiology is relatively low and the ablation targets stable, as the localization of the induced VTs was primarily driven by the remodeled structural substrate. Thus, personalized ventricular modeling with an average representation of infarct-remodeled electrophysiology may uncover most targets for VT ablation.
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http://dx.doi.org/10.3389/fphys.2019.00628 | DOI Listing |
Cell Signal
September 2025
School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, People's Republic of China.
Triple-negative breast cancer (TNBC) presents a formidable therapeutic challenge due to its aggressive behavior, molecular heterogeneity, and lack of actionable targets. This study identifies activation-induced cytidine deaminase (AID) as a pivotal epigenetic driver reprogramming the tumor microenvironment (TME) via non-canonical regulation of NOTCH signaling. Mechanistically, AID recruits histone acetyltransferase 1 (HAT1) to form a chromatin-remodeling complex that binds the JAG1 promoter region (-1.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Xianyang, China. Electronic address:
Pancreatic adenocarcinoma (PAAD) lacks effective therapies due to complex macromolecular signaling networks. Here, we identified the natural compound Trienomycin A (TA) as a potent binder and degrader of the key signaling adaptor protein Insulin Receptor Substrate 1 (IRS1), disrupting its macromolecular assembly in insulin-like growth pathways. Through integrated biochemical, cellular, and in vivo analyses, we demonstrated that TA directly bound the phosphotyrosine-binding (PTB) domain of IRS1, inducing proteasomal degradation of this critical macromolecular hub mediated by the E3 ubiquitin ligase FBXW8.
View Article and Find Full Text PDFInterdiscip Cardiovasc Thorac Surg
September 2025
Department of Electrophysiology, Abbott Inc, Chicago, IL.
We report the first use of the EnSite X system for intraoperative electrophysiological mapping during a robotic hybrid ablation (ROK-AF procedure) for long-standing persistent atrial fibrillation. Epicardial ablation targets were identified, and post-ablation electrical silencing was validated. Unlike conventional systems, its orientation-independent omnipolar technology provides directional activation vectors, high-resolution electrograms, and peak frequency analysis, thereby enhancing substrate characterisation.
View Article and Find Full Text PDFMed Oncol
September 2025
Department of Biotechnology, Institute of Engineering and Management, University of Engineering and Management, Kolkata, Kolkata, India.
Oligomeric proanthocyanidins (OPCs), condensed tannins found plentiful in grape seeds and berries, have higher bioavailability and therapeutic benefits due to their low degree of polymerization. Recent evidence places OPCs as effective modulators of cancer stem cell (CSC) plasticity and tumor growth. Mechanistically, OPCs orchestrate multi-pathway inhibition by destabilizing Wnt/β-catenin, Notch, PI3K/Akt/mTOR, JAK/STAT3, and Hedgehog pathways, triggering β-catenin degradation, silencing stemness regulators (OCT4, NANOG, SOX2), and stimulating tumor-suppressive microRNAs (miR-200, miR-34a).
View Article and Find Full Text PDFBeilstein J Nanotechnol
September 2025
B. I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, 220072 Minsk, Belarus.
In this study, silicon nanoparticles (NPs) were produced by pulsed laser ablation in a liquid, aiming to investigate the influence of a laser beam profile on the properties of the resultant NPs. Morphology, inner structure, and phase composition of the formed NPs were characterized by means of ultraviolet-visible spectroscopy, high-resolution transmission electron microscopy, and Raman and photoluminescence spectroscopies, and the correlation of the NP properties with the laser beam profile was studied. Three different beam profiles were selected, namely, a Bessel beam produced using an axicon, an annular profile formed using a combination of an axicon and a converging lens, and a Gaussian beam focused on the surface of a Si target using the same converging lens.
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