Search Results (112)

The apelin–ELABELA–APJ axis, collectively known as the apelinergic system, has emerged as a key regulator of cardiovascular homeostasis. Acting through G-protein-coupled mechanisms, it modulates vascular tone, cardiac contractility, angiogenesis, fluid balance, and metabolism. Growing evidence indicates that dysregulation of apelinergic signaling contributes to the development and progression of atherosclerosis, hypertension, and heart failure. Experimental studies demonstrate cardioprotective actions of apelin and ELABELA, including anti-fibrotic, anti-inflammatory, vasodilatory, and pro-angiogenic effects, whereas some findings suggest context-dependent pro-atherogenic or vasoconstrictive roles. Clinical data show that circulating apelinergic peptides vary across cardiovascular conditions, being upregulated in acute coronary syndromes and diminished in chronic ischemic or hypertensive disease. In heart failure, early compensatory activation is followed by progressive depletion, and low ELABELA levels correlate with disease severity. Moreover, the apelinergic system may exert anti-arrhythmic effects through modulation of myocardial electrophysiology and structural remodeling. Novel synthetic APJ agonists and stabilized peptide analogs show promising preclinical efficacy in reducing cardiac remodeling, improving contractility, and lowering blood pressure. Altogether, the apelinergic pathway represents a multifaceted modulator and a promising therapeutic target in cardiovascular medicine, warranting further translational studies to elucidate its diagnostic and treatment potential. Full article

Background: Intuitive inquiry meditation (Can-Hua-Tou) is a unique mental practice which differs from relaxation-based practices by continuously demanding intuitive inquiry. It emphasizes the doubt-driven self-interrogation, also referred to as Chan/Zen meditation. Nonetheless, its electrophysiological signature remains poorly characterized. Methods: We recorded 128-channel EEG from 20 male Buddhist monks (5–28 years Can-Hua-Tou experience) and 18 male novice lay practitioners (<0.5 year) during three counter-balanced eyes-closed blocks: Zen inquiry meditation (ZEN), a phonological control task silently murmuring “A-B-C-D” (ABCD), and passive resting state (REST). Power spectral density was computed for alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–45 Hz) bands and mapped across the scalp. Mixed-design ANOVAs and electrode-wise tests were corrected with false discovery rate (p < 0.05). Results: Alpha power increased globally with eyes closed, but condition- or group-specific effects did not survive FDR correction, indicating comparable relaxation in both cohorts. In contrast, monks displayed a robust beta augmentation, showing significantly higher beta over parietal-occipital leads than novices across all conditions. The most pronounced difference lay in the gamma band: monks exhibited trait-like fronto-parietal gamma elevations in all three conditions, with additional, though sub-threshold, increases during ZEN. Novices showed negligible beta or gamma modulation across tasks. No significant group × condition interaction emerged after correction, yet only experts expressed concurrent beta/gamma amplification during meditative inquiry. Conclusions: Long-term Can-Hua-Tou practice is associated with frequency-specific neural adaptations—stable high-frequency synchrony and state-dependent beta enhancement—consistent with Buddhist constructs of citta-ekāgratā (one-pointed concentration) and vigilance during self-inquiry. Unlike mindfulness styles that accentuate alpha/theta, Chan inquiry manifests an oscillatory profile dominated by beta–gamma dynamics, underscoring that different contemplative strategies sculpt distinct neurophysiological phenotypes. These findings advance contemplative neuroscience by linking intensive cognitive meditation to enduring high-frequency cortical synchrony. Future research integrating cross-frequency coupling analyses, source localization, and behavioral correlates of insight will further fully delineate the mechanisms underpinning this advanced contemplative expertise. Full article

While calcium (Ca²⁺) is a universal cellular messenger, the ionic properties of magnesium (Mg²⁺) make it less suited for rapid signaling and more for structural integrity. Still, besides being a passive player, Mg²⁺ is the only active Ca²⁺ antagonist, essential for tuning the efficacy of Ca²⁺-dependent cardiac excitation–contraction coupling (ECC) and for ensuring cardiac function robustness and stability. This review aims to provide a comprehensive framework to link the structural and molecular mechanisms of Mg²⁺/Ca²⁺ antagonistic binding across key proteins of the cardiac ECC machinery to their physiopathological relevance. The pervasive “dampening” effect of Mg²⁺ on ECC activity is exerted across various players and mechanisms, and lies in the ions’ physiological competition for multiple, flexible binding protein motifs across multiple compartments. Mg²⁺ profoundly modulates the cardiac action potential waveform by inhibiting the L-type Ca²⁺ channel Cav1.2, i.e., the key trigger of cardiac ryanodine receptor (RyR2) opening. Cytosolic Mg²⁺ favors RyR2 closed or inactive conformations not only through physical binding at specific sites, but also indirectly through modulation of RyR2 phosphorylation by Camk2d and PKA. RyR2 is also potently inhibited by luminal Mg²⁺, a vital mechanism in the cardiac setting for preventing excessive Ca²⁺ release during diastole. This mechanism, able to distinguish between Ca²⁺ and Mg²⁺, is mediated by luminal partners Calsequestrin 2 (CASQ2) and Triadin (TRDN). In addition, Mg²⁺ favors a rearrangement of the RyR2 cluster configuration that is associated with lower Ca²⁺ spark frequencies. Full article

The development of real-time learning assessment tools is hindered by an incomplete understanding of the underlying neural mechanisms. To address this gap, this study aimed to identify the specific neural correlates of implicit learning, a foundational process crucial for skill acquisition. We collected simultaneous electroencephalography and functional near-infrared spectroscopy data from thirty healthy adults (ages 21–29) performing a serial reaction time task designed to induce implicit learning. By capturing both electrophysiological and hemodynamic responses concurrently at shared locations, this dataset offers a unique opportunity to investigate neurovascular coupling during implicit learning and gain deeper insights into the neural mechanisms of learning. The dataset is categorized into two groups: participants who demonstrated implicit learning (based on post-experiment interviews) and those who did not. This dataset enables the identification of prominent brain regions, features, and temporal patterns associated with successful implicit learning. This identification will form the basis for future real-time learning assessment tools. Full article

In this study, we have performed 3D numerical simulations of the excitation and contraction of thin slab-like samples of myocardium tissue. The samples included a narrow region of almost non-excitable tissue simulating impaired myocardium. In the numerical experiments, we considered the heterogeneity of myocardium excitation and the ${\mathrm{Ca}}^{2+}$ activation of its contraction, as well as the orientation of the muscle fibers. Those characteristics varied throughout the thin wall of the sample. The simulations were performed in our numerical framework for the problems of cardiac electromechanics developed recently. The framework was previously tested for the benchmark problems in which formulations took into account only myocardium electrophysiology and passive mechanics. The study could be considered as an approbation of the framework performance with the fully coupled mathematical model of myocardium electromechanics. Here we dealt with the problems requiring a multiscale approach, taking into account cell-level electrophysiology, cell-level mechano-chemical processes, macromechanics (strain and stress) of the 3D sample, and interconnections between the levels. It was shown how the tissue heterogeneity and its strain affected the propagation of excitation–contraction waves in the sample, including, in particular, the formation of spiral waves. Full article

Microglia, as the immune guardians of the central nervous system (CNS), have the ability to maintain neural homeostasis, respond to environmental changes, and remodel the synaptic landscape. However, persistent microglial activation can lead to chronic neuroinflammation, which can alter neuronal signaling pathways, resulting in accelerated cognitive decline. Phosphoinositol 3-kinase (PI3K) has emerged as a critical driver, connecting inflammation to neurodegeneration, serving as the nexus of numerous intracellular processes that govern microglial activation. This review focuses on the relationship between PI3K signaling and microglial activation, which might lead to cognitive impairment, inflammation, or even neurodegeneration. The review delves into the components of the PI3K signaling cascade, isoforms, and receptors of PI3K, as well as the downstream effects of PI3K signaling, including its effectors such as protein kinase B (Akt) and mammalian target of rapamycin (mTOR) and the negative regulator phosphatase and tensin homolog (PTEN). Experiments have shown that the overproduction of certain cytokines, coupled with abnormal oxidative stress, is a consequence of poor PI3K regulation, resulting in excessive synapse pruning and, consequently, impacting learning and memory functions. The review also highlights the implications of autonomously activated microglia exhibiting M1/M2 polarization driven by PI3K on hippocampal, cortical, and subcortical circuits. Conclusions from behavioral studies, electrophysiology, and neuroimaging linking cognitive performance and PI3K activity were evaluated, along with new approaches to therapy using selective inhibitors or gene editing. The review concludes by highlighting important knowledge gaps, including the specific effects of different isoforms, the risks associated with long-term pathway modulation, and the limitations of translational potential, underscoring the crucial role of PI3K in mitigating cognitive impairment driven by neuroinflammation. Full article

This review investigates recent developments in cardiac mechano-electrical-fluid interaction (MEFI) modeling, with a focus on multiphysics simulation platforms and digital twin frameworks developed between 2015 and 2025. The purpose of the study is to assess how computational modeling methods—particularly finite element and immersed boundary techniques, monolithic and partitioned coupling schemes, and artificial intelligence (AI)-enhanced surrogate modeling—capture the integrated dynamics of cardiac electrophysiology, tissue mechanics, and hemodynamics. The goal is to evaluate the translational potential of MEFI models in clinical applications such as cardiac resynchronization therapy (CRT), arrhythmia classification, atrial fibrillation ablation, and surgical planning. Quantitative results from the literature demonstrate <5% error in pressure–volume loop predictions, >0.90 F1 scores in machine-learning-based arrhythmia detection, and <10% deviation in myocardial strain relative to MRI-based ground truth. These findings highlight both the promise and limitations of current MEFI approaches. While recent advances improve physiological fidelity and predictive accuracy, key challenges remain in achieving multiscale integration, model validation across diverse populations, and real-time clinical applicability. The review concludes by identifying future milestones for clinical translation, including regulatory model certification, standardization of validation protocols, and integration of patient-specific digital twins into electronic health record (EHR) systems. Full article

Introduction: Huntington’s disease (HD) disrupts cortico-striato-thalamocortical circuits decades before clinical onset. Electroencephalography (EEG) offers millisecond temporal resolution, low cost, and broad accessibility, yet its mechanistic and biomarker potential in HD remains underexplored. We conducted a mechanistic review to synthesize half a century of EEG findings, identify reproducible electrophysiological signatures, and outline translational next steps. Methods: Two independent reviewers searched PubMed, Scopus, Google Scholar, ResearchGate, and the Cochrane Library (January 1970–April 2025) using the terms “EEG” OR “electroencephalography” AND “Huntington’s disease”. Clinical trials published in English that reported raw EEG (not ERP-only) in human HD gene carriers were eligible. Abstract/title screening, full-text appraisal, and cross-reference mining yielded 22 studies (~700 HD recordings, ~600 controls). We extracted sample characteristics, acquisition protocols, spectral/connectivity metrics, and neuroclinical correlations. Results: Across diverse platforms, a consistent spectral trajectory emerged: (i) presymptomatic carriers show a focal 7–9 Hz (low-alpha) power loss that scales with CAG repeat length; (ii) early-manifest patients exhibit widespread alpha attenuation, delta–theta excess, and a flattened anterior-posterior gradient; (iii) advanced disease is characterized by global slow-wave dominance and low-voltage tracings. Source-resolved studies reveal early alpha hypocoherence and progressive delta/high-beta hypersynchrony, microstate shifts (A/B ↑, C/D ↓), and rising omega complexity. These electrophysiological changes correlate with motor burden, cognitive slowing, sleep fragmentation, and neurovascular uncoupling, and achieve 80–90% diagnostic accuracy in shallow machine-learning pipelines. Conclusions: EEG offers a coherent, stage-sensitive window on HD pathophysiology—from early thalamocortical disinhibition to late network fragmentation—and fulfills key biomarker criteria. Translation now depends on large, longitudinal, multi-center cohorts with harmonized high-density protocols, rigorous artifact control, and linkage to clinical milestones. Such infrastructure will enable the qualification of alpha-band restoration, delta-band hypersynchrony, and neurovascular coupling as pharmacodynamic readouts, fostering precision monitoring and network-targeted therapy in Huntington’s disease. Full article

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate that oxidizing agents reduce repolarizing currents, whereas reducing systems restore normal channel activity. Similarly, oxidative modifications of calcium-handling proteins amplify sarcoplasmic reticulum release and diastolic calcium leak. Understanding the precise redox-dependent modifications of cardiac ion channels would guide new possibilities for targeted therapies aimed at restoring electrophysiological homeostasis under oxidative stress, potentially alleviating myocardial infarction and cardiovascular dysfunction. Full article

Accurately monitoring coupled water–nitrogen stress is critical for wheat (Triticum aestivum L.) productivity under climate change. This study developed a machine learning framework utilizing multimodal leaf electrophysiological signals––intrinsic resistance, impedance, capacitive reactance, inductive reactance, and capacitance––to decouple water and nitrogen stress signatures in wheat. A parallel modelling strategy was implemented employing Gradient Boosting, Random Forest, and Ridge Regression, selecting the optimal algorithm per feature based on predictive performance. Controlled pot experiments revealed IZ as the paramount biomarker across leaf positions, indicating its sensitivity to ion flux perturbations under abiotic stress. Crucially, algorithm-feature specificity was identified: Ridge Regression excelled in modeling linear responses due to its superior noise suppression, while GB effectively captured nonlinear dynamics. Flag leaves during reproductive stages provided significantly more stable predictions compared to vegetative third leaves, aligning with their physiological primacy as source organs. This framework offers a robust, non-invasive approach for real-time water and nitrogen stress diagnostics in precision agriculture. Full article

Background/Objectives: G protein-coupled trace amine-associated receptors (TAARs) belong to a family of biogenic amine-sensing receptors. TAAR1 is the best-investigated receptor of this family, and TAAR1 agonists are already being tested in clinical studies for the treatment of schizophrenia, anxiety, and depression. Meanwhile, other TAARs (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9 in humans) are mostly known for their olfactory function, sensing innate odors. At the same time, there is growing evidence that these receptors may also be involved in brain function. TAAR8 is the least studied TAAR family member, and currently, there is no data on its function in the mammalian central nervous system. Methods: We generated triple knockout (tTAAR8-KO) mice lacking all murine Taar8 isoforms (Taar8a, Taar8b, and Taar8c) using CRISPR-Cas9 technology. In this study, we performed the first phenotyping of tTAAR8-KO mice for behavioral, electrophysiological, and neurochemical characteristics. Results: During the study, we found a number of alterations specific to tTAAR8-KO mice compared to controls. tTAAR8-KO mice demonstrated better short-term memory, more depressive-like behavior, and higher body temperature. Also, we observed changes in the dopaminergic system, brain electrophysiological activity, and adult neurogenic functions in mice lacking Taar8 isoforms. Conclusions: Based on the data obtained, it can be assumed that the physiological TAAR8 role is not limited only to the innate olfactory function, as previously proposed. TAAR8 could be involved in brain function, in particular in dopamine function regulation. Full article

To investigate how dysregulated transient receptor potential canonical channels (TRPCs) are associated with Alzheimer’s disease (AD), we challenged primary neurons with amyloid-β (Aβ). Both the naturally secreted or synthetic Aβ oligomers (AβOs) induced long-lasting increased TRPC3 and downregulated the TRPC6 expression in mature excitatory neurons (CaMKIIα-high) via a Ca²⁺-dependent calcineurin-coupled NFAT transcriptionally and calpain-mediated protein degradation, respectively. The TRPC3 expression was also found to be upregulated in pyramidal neurons of human AD brains. The selective downregulation of the Trpc6 gene induced synaptotoxicity, while no significant effect was observed from the Trpc3-targeting siRNA, suggesting potentially differential roles of TRPC3 and 6 in modulating the synaptic morphology and functions. Electrophysiological recordings of mouse hippocampal slices overexpressing TRPC3 revealed increased neuronal hyperactivity upon the TRPC3 channel activation by its agonist. Furthermore, the AβO-mediated synaptotoxicity appeared to be positively correlated with the degrees of the induced dendritic Ca²⁺ flux in neurons, which was completely prevented by the co-treatment with two pyrazole-based TRPC3-selective antagonists Pyr3 or Pyr10. Taken together, our findings suggest that the aberrantly upregulated TRPC3 is another ion channel critically contributing to the process of AβO-induced Ca²⁺ overload, neuronal hyperexcitation, and synaptotoxicity, thus representing a potential therapeutic target of AD. Full article

Background: Image-guided navigation has revolutionized precision cardiac interventions, yet current technologies face critical limitations in real-time guidance and procedural accuracy. Method: Here, we comprehensively evaluate state-of-the-art imaging modalities, from conventional fluoroscopy to emerging hybrid systems, analyzing their applications across coronary, structural, and electrophysiological interventions. Results: We demonstrate that novel approaches combining optical coherence tomography with near-infrared spectroscopy or fluorescence achieve unprecedented plaque characterization and procedural guidance through simultaneous structural and molecular imaging. Our analysis reveals key challenges, including imaging artifacts and resolution constraints, while highlighting recent technological solutions incorporating artificial intelligence and robotics. We show that non-imaging alternatives, such as fiber optic real-shape sensing and electromagnetic tracking, complement traditional techniques by providing real-time navigation without radiation exposure. This paper also discusses the integration of image-guided navigation techniques into augmented reality systems and patient-specific modeling, highlighting initial clinical studies that demonstrate their significant promise in reducing procedural times and improving accuracy. These findings establish a framework for next-generation cardiac interventions, emphasizing the critical role of multimodal imaging platforms enhanced by AI-driven decision support. Conclusions: We conclude that continued innovation in hybrid imaging systems, coupled with advances in automation, will be essential for optimizing procedural outcomes and expanding access to complex cardiac interventions. Full article

Pituitary cells are specialized cells located within the pituitary gland, a small, pea-sized gland situated at the base of the brain. Through the use of cellular electrophysiological techniques, the electrical properties of these cells have been revealed. This review paper aims to introduce the ion currents that are known to be functionally expressed in pituitary cells. These currents include a voltage-gated Na⁺ current (I_Na), erg-mediated K⁺ current (I_K(erg)), M-type K⁺ current (I_K(M)), hyperpolarization-activated cation current (I_h), and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel. The biophysical characteristics of the respective ion current were described. Additionally, we also provide explanations for the effect of various drugs or compounds on each of these currents. GH₃-cell exposure to GV-58 can increase the magnitude of I_Na with a concurrent rise in the inactivation time constant of the current. The presence of esaxerenone, an antagonist of the aldosterone receptor, directly suppresses the magnitude of peak and late I_Na. Risperidone, an atypical antipsychotic agent, is effective at suppressing the I_K(erg) amplitude directly, and di(2-ethylhexyl)-phthalate suppressed I_K(erg). Solifenacin and kynurenic acid can interact with the K_M channel to stimulate I_K(M), while carisbamate and cannabidiol inhibit the I_h amplitude activated by sustained hyperpolarization. Moreover, the presence of either rufinamide or QO-40 can enhance the activity of single BK_Ca channels. To summarize, alterations in ion currents within native pituitary cells or pituitary tumor cells can influence their functional activity, particularly in processes like stimulus–secretion coupling. The effects of small-molecule modulators, as demonstrated here, bear significance in clinical, therapeutic, and toxicological contexts. Full article

Background: Atrial flutter (AFL) is a macro-reentrant tachycardia classified as cavotricuspid isthmus (CTI)-dependent or non-CTI-dependent based on its reliance on the CTI for conduction. CTI dependence can present as type I ECG (sawtooth flutter waves in inferior leads and positive P-waves in V1) or type II ECG (absence of these characteristics). This study aimed to identify clinical and electrophysiological parameters to improve CTI dependence prediction in AFL. Methods: Patients at the Ulm University Heart Center between 2010 and 2019 with AFL undergoing electrophysiological studies and ablation were enrolled. Clinical and electrophysiological parameters such as age, gender, prior comorbidities, interventions, and medication use were analyzed. Results: The study included 383 patients, with 70% presenting with type I ECG AFL. CTI dependence was observed in 242 (90.3%) type I ECG patients and 52 (45.2%) type II ECG patients. CTI-dependent AFL patients were younger and had fewer comorbidities. Predictors for CTI dependence in type I ECG included male gender (p = 0.006), absence of beta-blocker use (p = 0.031), no prior atrial fibrillation (p = 0.035), and no prior pulmonary vein isolation (p < 0.001). In type II ECG, predictors for CTI dependence included younger age (p = 0.016), male gender (p = 0.007), absence of arterial hypertension (p = 0.036), and longer atrial cycle length (p < 0.001). Conclusions: Identifying clinical and electrophysiological parameters enhances the ability to predict CTI dependence in AFL, offering valuable insights for tailored diagnostic and therapeutic approaches. Coupling these parameters with ECG findings holds promise for refining prediction accuracy and optimizing patient care. Full article