Macrophages in Calcific Aortic Valve Disease: Paracrine and Juxtacrine Disease Drivers.

A significant role in the pathogenesis of CAVD is played by innate immunity cells, such as macrophages. In stenotic valves, macrophages have enhanced inflammatory activity, and the population's balance is shifted toward pro-inflammatory ones. Pro-inflammatory macrophages release cytokines, chemokines, and microRNA, which can directly affect the resident valvular cells and cause valve calcification.

Proteomic Profiling of Endothelial Cell Secretomes After Exposure to Calciprotein Particles Reveals Downregulation of Basement Membrane Assembly and Increased Release of Soluble CD59.

Calciprotein particles (CPPs) are essential circulating scavengers of excessive Ca and PO ions, representing a vehicle that removes them from the human body and precludes extraskeletal calcification. Having been internalised by endothelial cells (ECs), CPPs induce their dysfunction, which is accompanied by a remarkable molecular reconfiguration, although little is known about this process's extracellular signatures. Here, we applied ultra-high performance liquid chromatography-tandem mass spectrometry to perform a secretome-wide profiling of the cell culture supernatant from primary human coronary artery ECs (HCAECs) and internal thoracic artery ECs (HITAECs) treated with primary CPPs (CPP-P), secondary CPPs (CPP-S), magnesiprotein particles (MPPs), or Ca/Mg-free Dulbecco's phosphate-buffered saline (DPBS) for 24 h.

Citrullination Accompanies the Development of Carotid Atherosclerotic Plaques.

Background: Citrullination represents a post-translational modification primarily mediated by peptidylarginine deiminase (PADI) 2 and 4 and resulting in the conversion of positively charged peptidylarginine to neutrally charged peptidylcitrulline. Molecular consequences of citrullination include the generation of neoepitopes which provoke the production of autoantibodies implicated in the development of autoimmune diseases. As citrullination initiates, promotes, and is enhanced by aseptic inflammation which plays a pivotal role in atherosclerosis, we proposed that citrullination might accompany the development of atherosclerotic vascular disease.

Lipopolysaccharide pretreatment increases the sensitivity of the TRPV1 channel and promotes an anti-inflammatory phenotype of capsaicin-activated macrophages.

Background: The transient receptor potential vanilloid 1 (TRPV1) is well-established in neuronal function, yet its role in immune reactions remains enigmatic. The conflicting data on its inflammatory role, suggesting both pro-inflammatory and anti-inflammatory effects upon TRPV1 stimulation in immune cells, adds complexity. To unravel TRPV1 immunomodulatory mechanisms, we investigated how the TRPV1 agonist capsaicin influences lipopolysaccharide (LPS)-induced pro-inflammatory macrophage phenotypes.

Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction.

Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis-a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction.

The Global Track Concept for Assessment of Engaging Hill-Sachs Defects in Anterior Shoulder Instability.

Background: The glenoid track concept is used to determine preoperatively whether a Hill-Sachs defect is engaging or not. Currently, the glenoid track concept relies on measurements of bony structures as well as on the confines and elasticity of the rotator cuff as a reference point, which varies extensively among individuals and therefore limits the reliability and accuracy of this concept.

Purpose: To evaluate the reliability of the global track concept, which determines the angular distance of the Hill-Sachs defect from the center of the articular surface of the humeral head as a new reference point with the help of an automated image analysis software and 3-dimensional analysis of the humeral head.

Reliability of Manual Measurements Versus Semiautomated Software for Glenoid Bone Loss Quantification in Patients With Anterior Shoulder Instability.

Background: The presence of glenoid bone defects is indicative in the choice of treatment for patients with anterior shoulder instability. In contrast to traditional linear- and area-based measurements, techniques such as the consideration of glenoid concavity have been proposed and validated.

Purpose: To compare the reliability of linear (1-dimensional [1D]), area (2-dimensional [2D]), and concavity (3-dimensional [3D]) measurements to quantify glenoid bone loss performed manually and to analyze how automated measurements affect reliability.

Calciprotein Particles Induce Cellular Compartment-Specific Proteome Alterations in Human Arterial Endothelial Cells.

Calciprotein particles (CPPs) are indispensable scavengers of excessive Ca and PO ions in blood, being internalised and recycled by liver and spleen macrophages, monocytes, and endothelial cells (ECs). Here, we performed a pathway enrichment analysis of cellular compartment-specific proteomes in primary human coronary artery ECs (HCAEC) and human internal thoracic artery ECs (HITAEC) treated with primary (amorphous) or secondary (crystalline) CPPs (CPP-P and CPPs, respectively). Exposure to CPP-P and CPP-S induced notable upregulation of: (1) cytokine- and chemokine-mediated signaling, Ca-dependent events, and apoptosis in cytosolic and nuclear proteomes; (2) H and Ca transmembrane transport, generation of reactive oxygen species, mitochondrial outer membrane permeabilisation, and intrinsic apoptosis in the mitochondrial proteome; (3) oxidative, calcium, and endoplasmic reticulum (ER) stress, unfolded protein binding, and apoptosis in the ER proteome.

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity.

Major adverse cardiovascular events occurring upon coronary artery bypass graft surgery are typically accompanied by endothelial dysfunction. Total arterial revascularisation, which employs both left and right internal thoracic arteries instead of the saphenous vein to create a bypass, is associated with better mid- and long-term outcomes. We suggested that molecular profiles of human coronary artery endothelial cells (HCAECs) and human internal mammary artery endothelial cells (HITAECs) are coherent in terms of transcriptomic and proteomic signatures, which were then investigated by RNA sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively.

Expression of Ceramide-Metabolizing Enzymes in the Heart Adipose Tissue of Cardiovascular Disease Patients.

Here, we examined the expression of ceramide metabolism enzymes in the subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT) of 30 patients with coronary artery disease (CAD) and 30 patients with valvular heart disease (VHD) by means of quantitative polymerase chain reaction and fluorescent Western blotting. The EAT of patients with CAD showed higher expression of the genes responsible for ceramide biosynthesis (, , , , , , and ) and utilization (, ). PVAT was characterized by higher mRNA levels of , , , , and ceramide utilization enzyme ().

Comparison of the Patency and Regenerative Potential of Biodegradable Vascular Prostheses of Different Polymer Compositions in an Ovine Model.

The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility.

Binge-spectrum symptoms in their association with higher gestational weight gain.

Objective: Gestational weight gain (GWG) above or below recommendations is common and has implications for parent and infant health. Bulimia nervosa and binge-eating disorder during pregnancy have been associated with higher GWG. Yet, little research has examined the associations between binge-spectrum symptoms and GWG.

Endothelial Cell Markers Are Inferior to Vascular Smooth Muscle Cells Markers in Staining Vasa Vasorum and Are Non-Specific for Distinct Endothelial Cell Lineages in Clinical Samples.

Current techniques for the detection of vasa vasorum (VV) in vascular pathology include staining for endothelial cell (EC) markers such as CD31 or VE-cadherin. However, this approach does not permit an objective assessment of vascular geometry upon vasospasm and the clinical relevance of endothelial specification markers found in developmental biology studies remains unclear. Here, we performed a combined immunostaining of rat abdominal aorta (rAA) and human saphenous vein (hSV) for various EC or vascular smooth muscle cell (VSMC) markers and found that the latter (e.

Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure.

Background Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde-treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next-generation chemicals remain largely unknown. This study aimed to investigate the reasons behind the development of SVD in ethylene glycol diglycidyl ether-treated BHVs. Methods and Results Ten ethylene glycol diglycidyl ether-treated BHVs excised because of SVD, and 5 calcified aortic valves (AVs) replaced with BHVs because of calcific AV disease were collected and their proteomic profile was deciphered.

Controlled and Synchronised Vascular Regeneration upon the Implantation of Iloprost- and Cationic Amphiphilic Drugs-Conjugated Tissue-Engineered Vascular Grafts into the Ovine Carotid Artery: A Proteomics-Empowered Study.

Implementation of small-diameter tissue-engineered vascular grafts (TEVGs) into clinical practice is still delayed due to the frequent complications, including thrombosis, aneurysms, neointimal hyperplasia, calcification, atherosclerosis, and infection. Here, we conjugated a vasodilator/platelet inhibitor, iloprost, and an antimicrobial cationic amphiphilic drug, 1,5-bis-(4-tetradecyl-1,4-diazoniabicyclo [2.2.

Calciprotein Particles Cause Physiologically Significant Pro-Inflammatory Response in Endothelial Cells and Systemic Circulation.

Calciprotein particles (CPPs) represent an inherent mineral buffering system responsible for the scavenging of excessive Ca and PO ions in order to prevent extraskeletal calcification, although contributing to the development of endothelial dysfunction during the circulation in the bloodstream. Here, we performed label-free proteomic profiling to identify the functional consequences of CPP internalisation by endothelial cells (ECs) and found molecular signatures of significant disturbances in mitochondrial and lysosomal physiology, including oxidative stress, vacuolar acidification, accelerated proteolysis, Ca cytosolic elevation, and mitochondrial outer membrane permeabilisation. Incubation of intact ECs with conditioned medium from CPP-treated ECs caused their pro-inflammatory activation manifested by vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) upregulation and elevated release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1/ C-C motif ligand 2 (MCP-1/CCL2).

Endothelial Dysfunction in the Context of Blood-Brain Barrier Modeling.

Here, we discuss pathophysiological approaches to the defining of endothelial dysfunction criteria (i.e., endothelial activation, impaired endothelial mechanotransduction, endothelial-to-mesenchymal transition, reduced nitric oxide release, compromised endothelial integrity, and loss of anti-thrombogenic properties) in different in vitro and in vivo models.

[Screening analysis of proteolytic enzymes and their inhibitors in the leaflets of epoxy-treated bioprosthetic heart valves explanted due to dysfunction].

Bioprosthetic heart valves (BHVs) are known for their lower thrombogenicity rates and excellent hemodynamic parameters similar to native valves. However, the lifespan of these medical devices is limited to 15 years due to the structural valve degeneration. One of the mechanisms underlying functional impairment and calcification of BHVs includes proteolytic degradation of biomaterials.

Explanatory models of post-traumatic stress disorder (PTSD) and depression among Afghan refugees in Norway.

Background: The current situation in Afghanistan makes it likely that we are facing a new wave of Afghan refugees, warranting more knowledge about how to deal with mental health problems among them. This study aims to gain more knowledge on Explanatory Models (EM) of depression and post-traumatic stress disorders (PTSD) among Afghan refugees resettled in Norway.

Methods: We conducted six gender-separated, semi-structured focusgroup interviews based on vignettes with Afghan refugees (total N = 27).

Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease.

iCOPE With COVID-19: A Brief Telemental Health Intervention for Children and Adolescents During the COVID-19 Pandemic.

The COVID-19 pandemic has prompted extensive disruptions to the daily lives of children and adolescents worldwide, which has been associated with an increase in anxiety and depressive symptoms in youth. However, due to public health measures, in-person psychosocial care was initially reduced, causing barriers to mental health care access. This study investigated the feasibility, acceptability and preliminary effectiveness of iCOPE with COVID-19, a brief telemental health intervention for children and adolescents to address anxiety symptoms.

β-Arrestin 1 and 2 similarly influence μ-opioid receptor mobility and distinctly modulate adenylyl cyclase activity.

β-Arrestins are known to play a crucial role in GPCR-mediated transmembrane signaling processes. However, there are still many unanswered questions, especially those concerning the presumed similarities and differences of β-arrestin isoforms. Here, we examined the roles of β-arrestin 1 and β-arrestin 2 at different levels of μ-opioid receptor (MOR)-regulated signaling, including MOR mobility, internalization of MORs, and adenylyl cyclase (AC) activity.

Analysis and Forecast of the Poverty Rate in the Arctic Zone of the Republic of Sakha (Yakutia).

The article analyzes the indicators of the poverty level in the regions of the Arctic zone of the Russian Federation, and assesses the level of poverty and quality of life in the Arctic zone of Yakutia. The results of sociological studies on the level of poverty in the Arctic regions are presented as well as the measures for its reduction associated with addressing the problems of employment, increasing incomes of the population, and the development of traditional crafts.

Explanatory models and help-seeking for symptoms of PTSD and depression among Syrian refugees.

Objective: This study investigates how Syrian refugees explain and prefer to seek help for symptoms of post-traumatic stress disorder (PTSD) and depression.

Methods: We conducted five semi-structured focus group interviews based on a vignette-technique with Syrian refugees (n = 21 men, n = 10 women). The vignettes describe a fictional person suffering from symptoms of PTSD or depression in line with DSM-5 and ICD-10 criteria.

Wear patterns and dental functioning in an Early Cretaceous stegosaur from Yakutia, Eastern Russia.

Isolated stegosaurian teeth from the Early Cretaceous high-latitude (palaeolatitude estimate of N 62°- 66.5°) Teete locality in Yakutia (Eastern Siberia, Russia) are characterized by a labiolingually compressed, slightly asymmetrical and mesiodistally denticulated (9-14 denticles) crown, a pronounced ring-like cingulum, as well as a "complex network of secondary ridges". The 63 teeth (found during on-site excavation in 2012, 2017-2019 and screen-washing in 2017-2019) most likely belong to one species of a derived (stegosaurine) stegosaur.