Examining transfer of TERT to mitochondria under oxidative stress.

The primary role of telomerase is the lengthening of telomeres. Nonetheless, emerging evidence highlights additional functions of telomerase outside of the nucleus. Specifically, its catalytic subunit, TERT (Telomerase Reverse Transcriptase), is detected in the cytosol and mitochondria.

The Role of NOTCH Pathway Genes in the Inherited Susceptibility to Aortic Stenosis.

The NOTCH-signaling pathway is responsible for intercellular interactions and cell fate commitment. Recently, NOTCH pathway genes were demonstrated to play an important role in aortic valve development, leading to an increased calcified aortic valve disease (CAVD) later in life. Here, we further investigate the association between genetic variants in the NOTCH pathway genes and aortic stenosis in a case-control study of 90 CAVD cases and 4723 controls using target panel sequencing of full-length 20 genes from a NOTCH-related pathway (, , , , , , , , , , , , , , , , , , , ).

Treatment and management of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross-sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients.

Rational Design of Drugs Targeting G-Protein-Coupled Receptors: Ligand Search and Screening.

G protein-coupled receptors (GPCRs) are transmembrane proteins that participate in many physiological processes and represent major pharmacological targets. Recent advances in structural biology of GPCRs have enabled the development of drugs based on the receptor structure (structure-based drug design, SBDD). SBDD utilizes information about the receptor-ligand complex to search for suitable compounds, thus expanding the chemical space of possible receptor ligands without the need for experimental screening.

Rational Design of Drugs Targeting G-Protein-Coupled Receptors: A Structural Biology Perspective.

G protein-coupled receptors (GPCRs) play a key role in the transduction of extracellular signals to cells and regulation of many biological processes, which makes these membrane proteins one of the most important targets for pharmacological agents. A significant increase in the number of resolved atomic structures of GPCRs has opened the possibility of developing pharmaceuticals targeting these receptors via structure-based drug design (SBDD). SBDD employs information on the structure of receptor-ligand complexes to search for selective ligands without the need for an extensive high-throughput experimental ligand screening and can significantly expand the chemical space for ligand search.

Evaluating of Existing VTE Risk Scales in Glioma Patients.

Introduction: Postoperative venous thromboembolism (VTE) is a frequently occurring complication among glioma patients. Several risk assessment models (RAMs), including the Caprini RAM, the IMPROVE Risk Score, the IMPROVED VTE Risk Score, and the Padua Prediction Score, have not been validated within the glioma patient population. The purpose of this study was to assess the predictive accuracy of established VTE risk scales in patients with glioma.

Elderly Patients with Idiopathic Pulmonary Hypertension: Clinical Characteristics, Survival, and Risk Stratification in a Single-Center Prospective Registry.

Introduction: The predictive value of the risk stratification scales in elderly patients with IPAH might differ from that in younger patients. It is unknown whether young and older IPAH patients have the same survival dependence on PAH-specific therapy numbers. The aim of this study was to evaluate the prognostic relevance of risk stratification scales and PAH medication numbers in elderly IPAH patients in comparison with young IPAH patients.

Recognition, diagnosis, and operability assessment of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Early recognition and diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is crucial for improving prognosis and reducing the disease burden. Established clinical practice guidelines describe interventions for the diagnosis and evaluation of CTEPH, yet limited insight remains into clinical practice variation and barriers to care. The CTEPH global cross-sectional scientific survey (CLARITY) was developed to gather insights into the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs.

Unusual Oligomeric Laccase-like Oxidases from Ascomycete VKM F-3561 Polymerizing Phenylpropanoids and Phenolic Compounds under Neutral Environmental Conditions.

The unique oligomeric alkaliphilic laccase-like oxidases of the ascomycete VKM F-3561 (with molecular masses about 1035 and 870 kDa) were purified and characterized for the first time. The ability of the enzymes to oxidize phenylpropanoids and phenolic compounds under neutral environmental conditions with the formation of previously unknown di-, tri-, and tetrameric products of transformation was shown. The possibility to obtain industrially valuable compounds (dihydroxybenzyl alcohol and hydroxytyrosol) from caffeic acid using laccase-like oxidases of VKM F-3561 has been shown.

Treatment of Idiopathic Recurrent Pericarditis With Goflikicept: Phase II/III Study Results.

Background: Idiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disease. Interleukin (IL)-1α and IL-1β are the pivotal cytokines in the pathophysiology of acute pericarditis and its recurrence. We created a phase II/III study with a new IL-1 inhibitor-goflikicept in IRP.

Sympathetic Denervation and Pharmacological Stimulation of Parasympathetic Nervous System Prevent Pulmonary Vascular Bed Remodeling in Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5-2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis.

Surgical treatment of chronic thromboembolic pulmonary hypertension in combination with a left anterior descending artery myocardial bridge: A case report.

Pulmonary thromboendarterectomy is a potentially curative option for most patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, a special group of patients with CTEPH requires simultaneous cardiac procedures. We report a rare case of successful surgical treatment of a CTEPH patient with a left anterior descending artery myocardial bridge.

Inhibition of JAK1,2 Prevents Fibrotic Remodeling of Pulmonary Vascular Bed and Improves Outcomes in the Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism with poor clinical outcomes. Therapeutic approaches to prevention of fibrotic remodeling of the pulmonary vascular bed in CTEPH are limited. In this work, we tested the hypothesis that Janus kinase 1/2 (JAK1/2) inhibition with ruxolitinib might prevent and attenuate CTEPH in a rat model.

The Laccase of Myrothecium roridum VKM F-3565: A New Look at Fungal Laccase Tolerance to Neutral and Alkaline Conditions.

Most of the currently known fungal laccases show their maximum activity under acidic environmental conditions. It is known that a decrease in the activity of a typical laccase at neutral or alkaline pH values is the result of an increase in the binding of the hydroxide anion to the T2/T3 copper center, which prevents the transfer of an electron from the T1 Cu to the trinuclear copper center. However, evolutionary pressure has resolved the existing limitations in the catalytic mechanism of laccase, allowing such enzymes to be functionally active under neutral/alkaline pH conditions, thereby giving fungi an advantage for their survival.

Prediction of Aortic Stenosis Progression by F-FDG and F-NaF PET/CT in Different Aortic Valve Phenotypes.

Different imaging techniques, such as echocardiography (ECHO) and CT, allow to assess aortic stenosis (AS) severity and could be used to study its progression. But only PET/CT open opportunities to assess activity of valvular inflammation and calcification . The aim of this study was to assess prognostic value of valvular inflammation and calcification measured by F-FDG and F-NaF PET/CT in patients with tricuspid (TAV) and bicuspid aortic valve (BAV).

Simple Predictors for Cardiac Fibrosis in Patients with Type 2 Diabetes Mellitus: The Role of Circulating Biomarkers and Pulse Wave Velocity.

Cardiac fibrosis is the basis of structural and functional disorders in patients with diabetes mellitus (T2DM). A wide range of laboratory and instrumental methods is used for its prediction. The study aimed to identify simple predictors of cardiac fibrosis in patients with T2DM based on the analysis of circulating fibrosis biomarkers and arterial stiffness.

Case Report: Multiple Causes of Cardiac Death After the First Infusion of Atezolizumab: Histopathological and Immunohistochemical Findings.

Immune checkpoint inhibitors are promising agents for anticancer therapy. But despite their high efficacy in the treatment of solid tumors, there is still a problem with immune-related adverse events, especially cardiovascular complications with a very high mortality rate. Myocarditis or ischemic heart disease progression is not the only possible cause of cardiovascular death in patients treated with checkpoint inhibitors.

Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension.

Pulmonary embolism (PE) is the third most prevalent cardiovascular disease. It is associated with high in-hospital mortality and the development of acute and chronic complications. New approaches aimed at improving the prognosis of patients with PE are largely dependent on reliable animal models.

Case Report: Two New Cases of Autosomal-Recessive Hypertrophic Cardiomyopathy Associated With -Compound Heterozygous Variant.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary diseases, and it is associated with fatal complications. The clinical heterogeneity of HCM requires risk prediction models to identify patients at a high risk of adverse events. Most HCM cases are caused by mutations in genes encoding sarcomere proteins.

Myocardial PD-L1 Expression in Patients With Ischemic and Non-ischemic Heart Failure.

Immune checkpoints inhibitors are promising and wide-spread agents in anti-cancer therapy. However, despite their efficacy, these agents could cause cardiotoxicity, a rare but life-threatening event. In addition, there are still no well-described predictive factors for the development of immune-related adverse events and information on high risk groups.

A retrospective analysis of colchicine in combination with NSAIDs therapy in patients with systemic form of adult-onset Still's disease with serositis.

Objectives: Adult-onset Still's disease (AOSD) is increasingly viewed as autoinflammatory disease associated with the so-called inflammasomopathy. Proinflammatory cytokines, such as IL-18 and IL-1β, processed through the inflammasome machinery, play an important role in the pathogenesis of AOSD. AOSD is heterogenous, therefore there are two subtypes of the disease, systemic and articular, which probably imply different approaches for the treatment.