Long COVID: Pathophysiology, current concepts, and future directions.

Long COVID, an umbrella term referring to a variety of symptoms and clinical presentations that emerges in a subset of patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has a significant effect on quality of life and places a substantial burden on health care systems worldwide, straining financial and human resources. The pathophysiology of long COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system perturbation, autoimmunity, latent virus reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long COVID.

Cathelicidin Antimicrobial Peptide Levels in Atherosclerosis and Myocardial Infarction in Mice and Human.

Obesity represents a worldwide health challenge, and the condition is accompanied by elevated risk of cardiovascular diseases caused by metabolic dysfunction and proinflammatory adipokines. Among those, the immune-modulatory cathelicidin antimicrobial peptide (human: CAMP; murine: CRAMP) might contribute to the interaction of the innate immune system and metabolism in these settings. We investigated systemic CAMP/CRAMP levels in experimental murine models of atherosclerosis, myocardial infarction and cardiovascular patients.

Decreased circulating CTRP3 levels in acute and chronic cardiovascular patients.

C1q/TNF-related protein 3 (CTRP3) represents an adipokine with various metabolic and immune-regulatory functions. While circulating CTRP3 has been proposed as a potential biomarker for cardiovascular disease (CVD), current data on CTRP3 regarding coronary artery disease (CAD) remains partially contradictory. This study aimed to investigate CTRP3 levels in chronic and acute settings such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS).

Cellular and Systemic Effects of Micro- and Nanoplastics in Mammals-What We Know So Far.

Microplastics (MP) and nanoplastics (NP) are accumulating more and more in our environment and have been frequently detected in water and soil, but also in a variety of mainly marine organisms. Polymers such as polyethylene, polypropylene, and polystyrene are those most commonly found. Once in the environment, MP/NP are carriers for many other substances, which often convey toxic effects.

Development of a dual-component infection-resistant arterial replacement for small-caliber reconstructions: A proof-of-concept study.

Synthetic vascular grafts perform poorly in small-caliber (<6mm) anastomoses, due to intimal hyperplasia and thrombosis, whereas homografts are associated with limited availability and immunogenicity, and bioprostheses are prone to aneurysmal degeneration and calcification. Infection is another important limitation with vascular grafting. This study developed a dual-component graft for small-caliber reconstructions, comprising a decellularized tibial artery scaffold and an antibiotic-releasing, electrospun polycaprolactone (PCL)/polyethylene glycol (PEG) blend sleeve.

Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc).

Inflammation is a strong driver of atherosclerotic cardiovascular disease (ASCVD). There is a large unmet need for therapies that prevent or reduce excessive inflammation while avoiding systemic immunosuppression. We showed previously that selective inhibition of pro-inflammatory interleukin-6 (IL-6) trans-signalling by the fusion protein olamkicept (sgp130Fc) prevented and reduced experimental murine atherosclerosis in low-density lipoprotein receptor-deficient ( ) mice on a high-fat, high-cholesterol diet independently of low-density lipoprotein (LDL) cholesterol metabolism.

How sign language expertise can influence the effects of face masks on non-linguistic characteristics.

Face masks occlude parts of the face which hinders social communication and emotion recognition. Since sign language users are known to process facial information not only perceptually but also linguistically, examining face processing in deaf signers may reveal how linguistic aspects add to perceptual information. In general, signers could be born deaf or acquire hearing loss later in life.

Extracellular Ribosomal RNA Acts Synergistically with Toll-like Receptor 2 Agonists to Promote Inflammation.

Self-extracellular RNA (eRNA), which is released under pathological conditions from damaged tissue, has recently been identified as a new alarmin and synergistic agent together with toll-like receptor (TLR)2 ligands to induce proinflammatory activities of immune cells. In this study, a detailed investigation of these interactions is reported. The macrophage cell line J774 A.

Monocyte subpopulation profiling indicates CDK6-derived cell differentiation and identifies subpopulation-specific miRNA expression sets in acute and stable coronary artery disease.

Coronary artery disease (CAD) is a long-lasting inflammatory disease characterized by monocyte migration into the vessel wall leading to clinical events like myocardial infarction (MI). However, the role of monocyte subsets, especially their miRNA-driven differentiation in this scenario is still in its infancy. Here, we characterized monocyte subsets in controls and disease phenotypes of CAD and MI patients using flow cytometry and miRNA and mRNA expression profiling using RNA sequencing.

Polystyrene microplastic particles induce endothelial activation.

Due to its increasing production, durability and multiple applications, plastic is a material we encounter every day. Small plastic particles from the μm to the mm range are classified as microplastics and produced for cosmetic and medical products, but are also a result of natural erosion and decomposition of macroplastics. Although being omnipresent in our environment and already detected in various organisms, less is known about the effects of microplastics on humans in general, or on vascular biology in particular.

Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells.

The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ- and tissue-specific expression analysis by real-time PCR revealed a considerable Ctrp3 expression in various adipose tissue compartments; however, higher levels were detected in the aorta and in abundantly perfused tissues (bone marrow and the thyroid gland).

Maize Brittle Stalk2-Like3, encoding a COBRA protein, functions in cell wall formation and carbohydrate partitioning.

Carbohydrate partitioning from leaves to sink tissues is essential for plant growth and development. The maize (Zea mays) recessive carbohydrate partitioning defective28 (cpd28) and cpd47 mutants exhibit leaf chlorosis and accumulation of starch and soluble sugars. Transport studies with 14C-sucrose (Suc) found drastically decreased export from mature leaves in cpd28 and cpd47 mutants relative to wild-type siblings.

25th anniversary of the Berlin workshop on developmental toxicology: DevTox database update, challenges in risk assessment of developmental neurotoxicity and alternative methodologies in bone development and growth.

25 years after the first Berlin Workshop on Developmental Toxicity this 10th Berlin Workshop aimed to bring together international experts from authorities, academia and industry to consider scientific, methodologic and regulatory aspects in risk assessment of developmental toxicity and to debate alternative strategies in testing developmental effects in the future. Proposals for improvement of the categorization of developmental effects were discussed as well as the update of the DevTox database as valuable tool for harmonization. The development of adverse outcome pathways relevant to developmental neurotoxicity (DNT) was debated as a fundamental improvement to guide the screening and testing for DNT using alternatives to animal methods.

Deficiency of Nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 reduces atherosclerosis.

Atherosclerosis is crucially fueled by inflammatory pathways including pattern recognition receptor (PRR)-related signaling of the innate immune system. Currently, the impact of the cytoplasmic PRRs nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2 is incompletely characterized. We, therefore, generated Nod1/Nod2 double knockout mice on a low-density lipoprotein receptor (Ldlr)-deficient background (= LdlrNod1/2) which were subsequently analyzed regarding experimental atherosclerosis, lipid metabolism, insulin resistance and gut microbiota composition.

Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells.

The nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 are mammalian cytosolic pattern recognition receptors sensing bacterial peptidoglycan fragments in order to initiate cytokine expression and pathogen host defense. Since endothelial cells are relevant cells for pathogen recognition at the blood/tissue interface, we here analyzed the role of NOD1- and NOD2-dependently expressed microRNAs (miRNAs, miR) for cytokine regulation in murine pulmonary endothelial cells. The induction of inflammatory cytokines in response to NOD1 and NOD2 was confirmed by increased expression of tumour necrosis factor (Tnf)-α and interleukin (Il)-6.

The Lipopeptide MALP-2 Promotes Collateral Growth.

Beyond their role in pathogen recognition and the initiation of immune defense, Toll-like receptors (TLRs) are known to be involved in various vascular processes in health and disease. We investigated the potential of the lipopeptide and TLR2/6 ligand macrophage activating protein of 2-kDA (MALP-2) to promote blood flow recovery in mice. Hypercholesterolemic apolipoprotein E (Apoe)-deficient mice were subjected to microsurgical ligation of the femoral artery.

Evaluation of the predictive reliability of a new watershed health assessment method using the SWAT model.

The purpose of watershed assessments is to give information about conditions of water quality, stream morphology, and biological integrity to identify the sources of stressors and their impacts. In recent decades, different watershed assessment methods have been developed to evaluate the cumulative impacts of human activities on watershed health and the condition of aquatic systems. In the current research, we propose a new approach for assessing watershed vulnerability to contamination based on spatial analysis by using geographic information systems (GIS) and the analytic hierarchy process (AHP) technique.

A novel approach for assessing watershed susceptibility using weighted overlay and analytical hierarchy process (AHP) methodology: a case study in Eagle Creek Watershed, USA.

Watershed vulnerability and the characterization of potential risk are important inputs for decision support tools in assessing watershed health. Most previous studies have focused on the assessment of the environmental risk using physicochemical properties of surface water and mathematical models to predict the health of a watershed. Here, we present a new methodology for evaluating watershed vulnerability using the analytic hierarchy process (AHP) and weighted overlay analysis.

Heparan Sulfate-Editing Extracellular Sulfatases Enhance VEGF Bioavailability for Ischemic Heart Repair.

Rationale: Mechanistic insight into the inflammatory response after acute myocardial infarction may inform new molecularly targeted treatment strategies to prevent chronic heart failure.

Objective: We identified the sulfatase SULF2 in an in silico secretome analysis in bone marrow cells from patients with acute myocardial infarction and detected increased sulfatase activity in myocardial autopsy samples. SULF2 (Sulf2 in mice) and its isoform SULF1 (Sulf1) act as endosulfatases removing 6--sulfate groups from heparan sulfate (HS) in the extracellular space, thus eliminating docking sites for HS-binding proteins.

Maize Carbohydrate Partitioning Defective33 Encodes an MCTP Protein and Functions in Sucrose Export from Leaves.

To sustain plant growth, development, and crop yield, sucrose must be transported from leaves to distant parts of the plant, such as seeds and roots. To identify genes that regulate sucrose accumulation and transport in maize (Zea mays), we isolated carbohydrate partitioning defective33 (cpd33), a recessive mutant that accumulated excess starch and soluble sugars in mature leaves. The cpd33 mutants also exhibited chlorosis in the leaf blades, greatly diminished plant growth, and reduced fertility.

Elevated expression of the metalloproteinase ADAM8 associates with vascular diseases in mice and humans.

Background And Aims: Members of the family of a disintegrin and metalloproteinases (ADAMs) and their substrates have been previously shown to modulate the inflammatory response in cardiac diseases, but studies investigating the relevance of ADAM8 are still rare. Our aim is to provide evidence for the inflammatory dysregulation of ADAM8 in vascular diseases and its association with disease severity.

Methods: Western-type diet fed Apoe and Ldlr mice and artery ligation served as murine model for atherosclerosis and myocardial infarction, respectively.

Suppressor of Cytokine Signaling 1 is Involved in Gene Regulation Which Controls the Survival of Ly6C Monocytes in Mice.

Background/aims: Inflammatory processes are controlled by the fine-tuned balance of monocyte subsets. In mice, different subsets of monocytes can be distinguished by the expression of Ly6C that is highly expressed on inflammatory monocytes (Ly6C) and to a lesser extent on patrolling monocytes (Ly6C). Our previous study revealed an accumulation of Ly6C monocytes in atherosclerotic-prone mice bearing a deficiency in suppressor of cytokine signaling (SOCS)-1 leading to an increased atherosclerotic burden.

Variety matters: Diverse functions of monocyte subtypes in vascular inflammation and atherogenesis.

Monocytes are important mediators of the innate immunity by recognizing and attacking especially bacterial pathogens but also play crucial roles in various inflammatory diseases, including vascular inflammation and atherosclerosis. Maturation, differentiation and function of monocytes have been intensively explored for a long time in innumerable experimental and clinical studies. Monocytes do not represent a uniform cell type but could be further subdivided into subpopulations with distinct features and functions.

Statistical assessment of nonpoint source pollution in agricultural watersheds in the Lower Grand River watershed, MO, USA.

The water quality in many Midwestern streams and lakes is negatively impacted by agricultural activities. Although the agricultural inputs that degrade water quality are well known, the impact of these inputs varies as a function of geologic and topographic parameters. To better understand how a range of land use, geologic, and topographic factors affect water quality in Midwestern watersheds, we sampled surface water quality parameters, including nitrate, phosphate, dissolved oxygen, turbidity, bacteria, pH, specific conductance, temperature, and biotic index (BI) in 35 independent sub-watersheds within the Lower Grand River Watershed in northern Missouri.