Neuropathology and Inflammatory Cell Characterization in 10 Autoptic COVID-19 Brains

COVID-19 presents with a wide range of clinical neurological manifestations. It has been recognized that SARS-CoV-2 infection affects both the central and peripheral nervous system, leading to smell and taste disturbances; acute ischemic and hemorrhagic cerebrovascular disease; encephalopathies and seizures; and causes most surviving patients to have long lasting neurological symptoms. Despite this, typical neuropathological features associated with the infection have still not been identified. Studies of post-mortem examinations of the cerebral cortex are obtained with difficulty due to laboratory safety concerns. In addition, they represent cases with different neurological symptoms, age or comorbidities, thus a larger number of brain autoptic data from multiple institutions would be crucial. Histopathological findings described here are aimed to increase the current knowledge on neuropathology of COVID-19 patients. We report post-mortem neuropathological findings of ten COVID-19 patients. A wide range of neuropathological lesions were seen. The cerebral cortex of all patients showed vascular changes, hyperemia of the meninges and perivascular inflammation in the cerebral parenchyma with hypoxic neuronal injury. Perivascular lymphocytic inflammation of predominantly CD8-positive T cells mixed with CD68-positive macrophages, targeting the disrupted vascular wall in the cerebral cortex, cerebellum and pons were seen. Our findings support recent reports highlighting a role of microvascular injury in COVID-19 neurological manifestations.

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Neutrophil Extracellular Traps in Periodontitis

Cells ◽

10.3390/cells9061494 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1494 ◽

Cited By ~ 1

Author(s):

Antonio Magán-Fernández ◽

Sarmad Muayad Rasheed Al-Bakri ◽

Francisco O’Valle ◽

Cristina Benavides-Reyes ◽

Francisco Abadía-Molina ◽

...

Keyword(s):

Current Knowledge ◽

Decisive Role ◽

Neutrophil Extracellular Traps ◽

Gingival Tissue ◽

Multifactorial Disease ◽

Extracellular Traps ◽

Wide Range ◽

Neutrophil Response ◽

Inflammatory Component

Neutrophils are key cells of the immune system and have a decisive role in fighting foreign pathogens in infectious diseases. Neutrophil extracellular traps (NETs) consist of a mesh of DNA enclosing antimicrobial peptides and histones that are released into extracellular space following neutrophil response to a wide range of stimuli, such as pathogens, host-derived mediators and drugs. Neutrophils can remain functional after NET formation and are important for periodontal homeostasis. Periodontitis is an inflammatory multifactorial disease caused by a dysbiosis state between the gingival microbiome and the immune response of the host. The pathogenesis of periodontitis includes an immune-inflammatory component in which impaired NET formation and/or elimination can be involved, contributing to an exacerbated inflammatory reaction and to the destruction of gingival tissue. In this review, we summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis.

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Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

Biomolecules ◽

10.3390/biom10121648 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1648

Author(s):

Daniel Liedtke ◽

Christine Hofmann ◽

Franz Jakob ◽

Eva Klopocki ◽

Stephanie Graser

Keyword(s):

Alkaline Phosphatase ◽

Clinical Symptoms ◽

Current Knowledge ◽

Systemic Disease ◽

Loss Of Function ◽

Inorganic Pyrophosphate ◽

Wide Range ◽

Mineralization Processes ◽

Tissue Nonspecific Alkaline Phosphatase

Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.

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Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

Clinical Chemistry ◽

10.1373/clinchem.2012.199711 ◽

2013 ◽

Vol 59 (8) ◽

pp. 1166-1174 ◽

Cited By ~ 69

Author(s):

Fina Lovren ◽

Subodh Verma

Keyword(s):

Endothelial Cells ◽

Cardiovascular Diseases ◽

Endothelial Dysfunction ◽

Vascular Endothelial Cells ◽

Current Knowledge ◽

Early Event ◽

Prognostic Information ◽

Vascular Events ◽

Wide Range

BACKGROUND Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation. CONTENT This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells. SUMMARY MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.

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Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽

10.1093/glycob/cwaa110 ◽

2020 ◽

Author(s):

Kaitlyn A Dorsett ◽

Michael P Marciel ◽

Jihye Hwang ◽

Katherine E Ankenbauer ◽

Nikita Bhalerao ◽

...

Keyword(s):

Cancer Cells ◽

Translational Regulation ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Sialic Acids ◽

Invasion Resistance ◽

Cell Behaviors ◽

Molecular Events ◽

Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

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Role of active patient involvement in undergraduate medical education: a systematic review

BMJ Open ◽

10.1136/bmjopen-2020-037217 ◽

2020 ◽

Vol 10 (7) ◽

pp. e037217

Author(s):

Stijntje Willemijn Dijk ◽

Edwin Johan Duijzer ◽

Matthias Wienold

Keyword(s):

Systematic Review ◽

Medical Education ◽

Undergraduate Medical Education ◽

Patient Involvement ◽

Current Knowledge ◽

Daily Practice ◽

Pubmed Database ◽

Wide Range ◽

Active Patient

ObjectivesTo identify the scope of active patient involvement in medical education, addressing the current knowledge gaps relating to rationale and motivation for involvement, recruitment and preparation, roles, learning outcomes and key procedural contributors.MethodsThe authors performed a systematic search of the PubMed database of publications between 2003 and 2018. Original studies in which patients take on active roles in the development, delivery or evaluation of undergraduate medical education and written in English were eligible for inclusion. Included studies’ references were searched for additional articles. Quality of papers was assessed using the Mixed Methods Appraisal Tool.Results49 articles were included in the review. Drivers for patient involvement included policy requirements and patients’ own motivations to contribute to society and learning. Patients were engaged in a variety of educational settings in and outside of the hospital. The vast majority of studies describe patients taking on the role of a patient teacher and formative assessor. More recent studies suggest that patients are increasingly involved in course and curriculum development, student selection and summative assessment. The new body of empirical evidence shows the wide range of learning objectives was pursued through patient participation, including competencies as professional, communicator, collaborator, leader and health advocate, but not scholar. Measures to support sustainable patient involvement included longitudinal institutional incorporation, patient recruitment and/or training, resource support and clear commitment by faculty. The importance and advantages of patient involvement were highlighted by students, faculty and patients themselves; however, organisations must continue to consider, monitor and take steps to mitigate any potential harms to patients and students.DiscussionThis systematic review provides new knowledge and practical insights to physicians and faculty on how to incorporate active patient involvement in their institutions and daily practice, and provides suggested action points to patient organisations wishing to engage in medical education.

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Stomatal conductance scales with petiole xylem traits in Populus genotypes

Functional Plant Biology ◽

10.1071/fp15336 ◽

2016 ◽

Vol 43 (6) ◽

pp. 553 ◽

Cited By ~ 5

Author(s):

Caroline A. Brocious ◽

Uwe G. Hacke

Keyword(s):

Stomatal Conductance ◽

Current Knowledge ◽

Hybrid Poplar ◽

Leaf Size ◽

Exchange Capacity ◽

Vein Density ◽

Wide Range ◽

Major Vein ◽

Size And Morphology

Progress has been made in linking water transport in leaves with anatomical traits. However, most of our current knowledge about these links is based on studies that sampled phylogenetically distant species and covered a wide range of leaf size and morphology. Here we studied covariation of leaf anatomical traits and hydraulic capacity in five closely related hybrid poplar genotypes. Variation in stomatal conductance and leaf hydraulic conductance was not linked to vein density or other anatomical lamina properties. A strong correlation was found between stomatal conductance and the transport capacity of the petiole, estimated from the diameter and number of xylem vessels. An inverse relationship existed between leaf size and major vein density. The role of bundle sheath extensions is discussed. Our data suggests that petiole xylem is an important predictor of gas exchange capacity in poplar leaves.

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Lysosome function in glomerular health and disease

Cell and Tissue Research ◽

10.1007/s00441-020-03375-7 ◽

2021 ◽

Author(s):

Catherine Meyer-Schwesinger

Keyword(s):

Current Knowledge ◽

Lysosomal Storage Diseases ◽

Cell Types ◽

Lysosomal Storage ◽

Membrane Repair ◽

Glomerular Cell ◽

Wide Range ◽

Center Position ◽

Health And Disease

AbstractThe lysosome represents an important regulatory platform within numerous vesicle trafficking pathways including the endocytic, phagocytic, and autophagic pathways. Its ability to fuse with endosomes, phagosomes, and autophagosomes enables the lysosome to break down a wide range of both endogenous and exogenous cargo, including macromolecules, certain pathogens, and old or damaged organelles. Due to its center position in an intricate network of trafficking events, the lysosome has emerged as a central signaling node for sensing and orchestrating the cells metabolism and immune response, for inter-organelle and inter-cellular signaling and in membrane repair. This review highlights the current knowledge of general lysosome function and discusses these findings in their implication for renal glomerular cell types in health and disease including the involvement of glomerular cells in lysosomal storage diseases and the role of lysosomes in nongenetic glomerular injuries.

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The Causal Relationship between Endothelin-1 and Hypertension: Focusing on Endothelial Dysfunction, Arterial Stiffness, Vascular Remodeling, and Blood Pressure Regulation

Life ◽

10.3390/life11090986 ◽

2021 ◽

Vol 11 (9) ◽

pp. 986

Author(s):

Krasimir Kostov

Keyword(s):

Blood Pressure ◽

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Structural Changes ◽

Vascular Wall ◽

Low Grade ◽

Endothelin 1 ◽

Vascular Regulation ◽

Wide Range

Hypertension (HTN) is one of the most prevalent diseases worldwide and is among the most important risk factors for cardiovascular and cerebrovascular complications. It is currently thought to be the result of disturbances in a number of neural, renal, hormonal, and vascular mechanisms regulating blood pressure (BP), so crucial importance is given to the imbalance of a number of vasoactive factors produced by the endothelium. Decreased nitric oxide production and increased production of endothelin-1 (ET-1) in the vascular wall may promote oxidative stress and low-grade inflammation, with the development of endothelial dysfunction (ED) and increased vasoconstrictor activity. Increased ET-1 production can contribute to arterial aging and the development of atherosclerotic changes, which are associated with increased arterial stiffness and manifestation of isolated systolic HTN. In addition, ET-1 is involved in the complex regulation of BP through synergistic interactions with angiotensin II, regulates the production of catecholamines and sympathetic activity, affects renal hemodynamics and water–salt balance, and regulates baroreceptor activity and myocardial contractility. This review focuses on the relationship between ET-1 and HTN and in particular on the key role of ET-1 in the pathogenesis of ED, arterial structural changes, and impaired vascular regulation of BP. The information presented includes basic concepts on the role of ET-1 in the pathogenesis of HTN without going into detailed analyses, which allows it to be used by a wide range of specialists. Also, the main pathological processes and mechanisms are richly illustrated for better understanding.

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Role of Carnitine in Non-alcoholic Fatty Liver Disease and Other Related Diseases: An Update

Frontiers in Medicine ◽

10.3389/fmed.2021.689042 ◽

2021 ◽

Vol 8 ◽

Author(s):

Na Li ◽

Hui Zhao

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Therapeutic Strategy ◽

Current Knowledge ◽

Alcoholic Fatty Liver ◽

Wide Range ◽

Multiple Hit ◽

Alcoholic Fatty Liver Disease

Carnitine is an amino acid-derived substance that coordinates a wide range of biological processes. Such functions include transport of long-chain fatty acids from the cytoplasm to the mitochondrial matrix, regulation of acetyl-CoA/CoA, control of inter-organellar acyl traffic, and protection against oxidative stress. Recent studies have found that carnitine plays an important role in several diseases, including non-alcoholic fatty liver disease (NAFLD). However, its effect is still controversial, and its mechanism is not clear. Herein, this review provides current knowledge on the biological functions of carnitine, the “multiple hit” impact of carnitine on the NAFLD progression, and the downstream mechanisms. Based on the “multiple hit” hypothesis, carnitine inhibits β-oxidation, improves mitochondrial dysfunction, and reduces insulin resistance to ameliorate NAFLD. L-carnitine may have therapeutic role in liver diseases including non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, alcoholic fatty liver disease, and viral hepatitis. We also discuss the prospects of L-carnitine supplementation as a therapeutic strategy in NAFLD and related diseases, and the factors limiting its widespread use.

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The function of S-nitrosothiols during abiotic stress in plants

Journal of Experimental Botany ◽

10.1093/jxb/erz197 ◽

2019 ◽

Vol 70 (17) ◽

pp. 4429-4439 ◽

Cited By ~ 18

Author(s):

Juan C Begara-Morales ◽

Mounira Chaki ◽

Raquel Valderrama ◽

Capilla Mata-Pérez ◽

Maria N Padilla ◽

...

Keyword(s):

Abiotic Stress ◽

Current Knowledge ◽

Stomatal Closure ◽

Cysteine Residue ◽

Detection Methods ◽

Plant Responses ◽

Wide Range ◽

Signaling Events

Abstract Nitric oxide (NO) is an active redox molecule involved in the control of a wide range of functions integral to plant biology. For instance, NO is implicated in seed germination, floral development, senescence, stomatal closure, and plant responses to stress. NO usually mediates signaling events via interactions with different biomolecules, for example the modulation of protein functioning through post-translational modifications (NO-PTMs). S-nitrosation is a reversible redox NO-PTM that consists of the addition of NO to a specific thiol group of a cysteine residue, leading to formation of S-nitrosothiols (SNOs). SNOs are more stable than NO and therefore they can extend and spread the in vivo NO signaling. The development of robust and reliable detection methods has allowed the identification of hundreds of S-nitrosated proteins involved in a wide range of physiological and stress-related processes in plants. For example, SNOs have a physiological function in plant development, hormone metabolism, nutrient uptake, and photosynthesis, among many other processes. The role of S-nitrosation as a regulator of plant responses to salinity and drought stress through the modulation of specific protein targets has also been well established. However, there are many S-nitrosated proteins that have been identified under different abiotic stresses for which the specific roles have not yet been identified. In this review, we examine current knowledge of the specific role of SNOs in the signaling events that lead to plant responses to abiotic stress, with a particular focus on examples where their functions have been well characterized at the molecular level.

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