Astrocyte TrkB promotes brain injury and edema formation in ischemic stroke.

Following ischemic stroke astrocytes undergo rapid molecular and functional changes that may accentuate tissue damage. In this study we identified the neurotrophin receptor TrkB in astrocytes as a key promoter of acute CNS injury in ischemic stroke. In fact, TrkB protein was strongly upregulated in astrocytes after human and experimental stroke, and transgenic mice lacking astrocyte TrkB displayed significantly smaller lesion volume, lower brain atrophy and better motor performance than control animals after transient middle cerebral artery occlusion.

Ablation of the epicardial substrate in patients with long-QT syndrome at risk of sudden death.

Sudden cardiac death remains a critical public health concern globally, affecting millions annually. Recent advances in cardiac arrhythmia mapping have demonstrated that the ventricular epicardial region has a critical arrhythmogenic role in some inherited cardiogenetic diseases. Among these, long-QT syndrome (LQTS) exposes patients to the risk of life-threatening arrhythmic events.

The "arrhythmic" presentation of peripartum cardiomyopathy: case series and critical review of the literature.

Peripartum Cardiomyopathy (PPCM) is a polymorphic myocardial disease occurring late during pregnancy or early after delivery. While reduced systolic function and heart failure (HF) symptoms have been widely described, there is still a lack of reports about the arrhythmic manifestations of the disease. Most importantly, a broad range of unidentified pre-existing conditions, which may be missed by general practitioners and gynecologists, must be considered in differential diagnosis.

High-risk Brugada syndrome: factors associated with arrhythmia recurrence and benefits of epicardial ablation in addition to implantable cardioverter defibrillator implantation.

Aims: This study aims to evaluate the prognostic impact of the arrhythmogenic substrate size in symptomatic Brugada syndrome (BrS) as well as to validate the long-term safety and effectiveness of epicardial radiofrequency ablation (RFA) compared with no-RFA group.

Methods And Results: In this prospective investigational long-term registry study, 257 selected symptomatic BrS patients with implantable cardioverter defibrillator (ICD) implantation were included. Among them, 206 patients underwent epicardial RFA and were monitored for over 5 years post-ablation (RFA group), while 51 patients received only ICD implantation declining RFA.

Challenges in Brugada Syndrome Stratification: Investigating Mutation Localization and Clinical Phenotypes.

Brugada Syndrome (BrS) is a genetic heart condition linked to sudden cardiac death. Though the gene is primarily associated with BrS, there is a lack of comprehensive studies exploring the connection between mutation locations and the clinical presentations of the syndrome. This study aimed to address this gap and gain further understanding of the syndrome.

Electrocardiographic temporo-spatial assessment of depolarization and repolarization changes after epicardial arrhythmogenic substrate ablation in Brugada syndrome.

Aims: In Brugada syndrome (BrS), with spontaneous or ajmaline-induced coved ST elevation, epicardial electro-anatomic potential duration maps (epi-PDMs) were detected on a right ventricle (RV) outflow tract (RVOT), an arrhythmogenic substrate area (AS area), abolished by epicardial-radiofrequency ablation (EPI-AS-RFA). Novel CineECG, projecting 12-lead electrocardiogram (ECG) waveforms on a 3D heart model, previously localized depolarization forces in RV/RVOT in BrS patients. We evaluate 12-lead ECG and CineECG depolarization/repolarization changes in spontaneous type-1 BrS patients before/after EPI-AS-RFA, compared with normal controls.

Deep learning unmasks the ECG signature of Brugada syndrome.

One in 10 cases of sudden cardiac death strikes without warning as the result of an inherited arrhythmic cardiomyopathy, such as Brugada Syndrome (BrS). Normal physiological variations often obscure visible signs of this and related life-threatening channelopathies in conventional electrocardiograms (ECGs). Sodium channel blockers can reveal previously hidden diagnostic ECG features, however, their use carries the risk of life-threatening proarrhythmic side effects.

Unravelling Novel Mutations Linked to Brugada Syndrome: Functional, Structural, and Genetic Insights.

Brugada Syndrome (BrS) is a rare inherited cardiac arrhythmia causing potentially fatal ventricular tachycardia or fibrillation, mainly occurring during rest or sleep in young individuals without heart structural issues. It increases the risk of sudden cardiac death, and its characteristic feature is an abnormal ST segment elevation on the ECG. While BrS has diverse genetic origins, a subset of cases can be conducted to mutations in the gene, which encodes for the Nav1.

Nanobodies counteract the toxicity of an amyloidogenic light chain by stabilizing a partially open dimeric conformation.

Light chain amyloidosis (AL) is a systemic disease where fibrillar deposition of misfolded immunoglobulin light chains (LCs) severely affects organ function and results in poor prognosis for patients, especially when heart involvement is severe. Particularly relevant in this context is the cardiotoxicity exerted by still uncharacterized soluble LC species. Here, with the final goal of identifying alternative therapeutic strategies to tackle AL amyloidosis, we produced five llama-derived nanobodies (Nbs) specific against H3, a well-characterized amyloidogenic and cardiotoxic LC from an AL patient with severe cardiac involvement.

Interplay of Modified Sialic Acid Inhibitors and the Human Parainfluenza Virus 1 Hemagglutinin-Neuraminidase Active Site.

In the search for effective antivirals against Paramyxoviridae, the dynamics of human parainfluenza virus type 1 hemagglutinin-neuraminidase (hPIV1-HN) inhibition offers a promising perspective. This study focuses on the potential of C5- and C4-modified 2,3-unsaturated sialic acid (DANA) inhibitors and highlights their interaction with the hPIV1-HN enzyme. We show that a strategic substitution, replacing the C5 isopropyl group in BCX 2798 with a trifluoroacetyl function, increases inhibitory potency 3- to 4-fold.

Arrhythmogenic substrate elimination for safe testosterone therapy in symptomatic Brugada syndrome patients.

Background: Brugada Syndrome (BrS) is a cardiogenetic disease known for its association with sudden cardiac death (SCD) in individuals with structurally normal hearts. The prevalence of BrS is higher in males, who also face a greater risk of SCD. Its higher prevalence and worse outcome in male subjects may be due to testosterone effects on ion channels expression and function.

The Cryo-EM STRUCTURE of Renal Amyloid Fibril Suggests Structurally Homogeneous Multiorgan Aggregation in AL Amyloidosis.

Immunoglobulin light chain amyloidosis (AL) is caused by the aberrant production of amyloidogenic light chains (LC) that accumulate as amyloid deposits in vital organs. Distinct LC sequences in each patient yield distinct amyloid structures. However different tissue microenvironments may also cause identical protein precursors to adopt distinct amyloid structures.

Analysis of the intramolecular 1,7-lactone of N-acetylneuraminic acid using HPLC-MS: relationship between detection and stability.

A subclass of the sialic acid family consists of intramolecular lactones that may function as key indicators of physiological and pathological states. However, the existence of these compounds in free form is highly improbable, since they are unlikely to exist in an aqueous solution due to their lability. Current analytical method used to detect them in biological fluids has not recognized their reactivity in solution and is prone to misidentification.

Automated Patch-Clamp and Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Synergistic Approach in the Study of Brugada Syndrome.

The development of high-throughput automated patch-clamp technology is a recent breakthrough in the field of Brugada syndrome research. Brugada syndrome is a heart disorder marked by abnormal electrocardiographic readings and an elevated risk of sudden cardiac death due to arrhythmias. Various experimental models, developed either in animals, cell lines, human tissue or computational simulation, play a crucial role in advancing our understanding of this condition, and developing effective treatments.

Design, Synthesis, and Antiviral Evaluation of Sialic Acid Derivatives as Inhibitors of Newcastle Disease Virus Hemagglutinin-Neuraminidase: A Translational Study on Human Parainfluenza Viruses.

Global infections with viruses belonging to the , such as Newcastle disease virus (NDV) or human parainfluenza viruses (hPIVs), pose a serious threat to animal and human health. NDV-HN and hPIVs-HN (HN hemagglutinin-neuraminidase) share a high degree of similarity in catalytic site structures; therefore, the development of an efficient experimental NDV host model (chicken) may be informative for evaluating the efficacy of hPIVs-HN inhibitors. As part of the broad research in pursuit of this goal and as an extension of our published work on antiviral drug development, we report here the biological results obtained with some newly synthesized C4- and C5-substituted 2,3-unsaturated sialic acid derivatives against NDV.

Right ventricular epicardial arrhythmogenic substrate in long-QT syndrome patients at risk of sudden death.

Aims: The long-QT syndrome (LQTS) represents a leading cause of sudden cardiac death (SCD). The aim of this study was to assess the presence of an underlying electroanatomical arrhythmogenic substrate in high-risk LQTS patients.

Methods And Results: The present study enrolled 11 consecutive LQTS patients who had experienced frequent implantable cardioverter-defibrillator (ICD discharges triggered by ventricular fibrillation (VF).

Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α.

Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia.

Neu3 Sialidase Activates the RISK Cardioprotective Signaling Pathway during Ischemia and Reperfusion Injury (IRI).

Coronary reperfusion strategies are life-saving approaches to restore blood flow to cardiac tissue after acute myocardial infarction (AMI). However, the sudden restoration of normal blood flow leads to ischemia and reperfusion injury (IRI), which results in cardiomyoblast death, irreversible tissue degeneration, and heart failure. The molecular mechanism of IRI is not fully understood, and there are no effective cardioprotective strategies to prevent it.

Cu(II) Binding Increases the Soluble Toxicity of Amyloidogenic Light Chains.

Light chain amyloidosis (AL) is caused by the aberrant overproduction of immunoglobulin light chains (LCs). The resulting abnormally high LC concentrations in blood lead to deposit formation in the heart and other target organs. Organ damage is caused not only by the accumulation of bulky amyloid deposits, but extensive clinical data indicate that circulating soluble LCs also exert cardiotoxic effects.