The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: May 28, 2020

Lactoferrin is a nutrient classically found in mammalian milk. It binds iron and transferred into between cells, serum, bile cerebrospinal fluid, via variety of receptors. has important immunological properties, both antibacterial antiviral. In particular, there evidence that it can bind to at least some the receptors used by coronaviruses thereby block their entry. may consequently be preventive therapeutic value during present COVID-19 pandemic.

Language: Английский

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A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(4), P. 537 - 559

Published: Feb. 23, 2022

Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype COVID-19), is a relatively frequent consequence SARS-CoV-2 infection, in which symptoms such breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions the blood coagulation system) persist long after initial infection. It bears similarities other post-viral syndromes, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this separate disease entity, refer it under broad terminology ‘COVID’, although its demographics are quite different from those acute COVID-19. A few years ago, we discovered that fibrinogen can clot into an anomalous ‘amyloid’ form fibrin (like β-rich amyloids prions) resistant proteolysis (fibrinolysis). The result, strongly manifested platelet-poor plasma (PPP) individuals with Long COVID, extensive amyloid microclots persist, entrap proteins, may lead production various autoantibodies. These more-or-less easily measured PPP stain thioflavin T simple fluorescence microscope. Although multifarious, here argue ability these (fibrinaloids) block up capillaries, thus limit passage red cells hence O2 exchange, actually underpin majority symptoms. Consistent this, preliminary report, has been shown suitable closely monitored ‘triple’ anticoagulant therapy leads removal also removes Fibrin represent novel potentially important target for both understanding treatment related disorders.

Language: Английский

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The biology of ergothioneine, an antioxidant nutraceutical

Nutrition Research Reviews, Journal Year: 2020, Volume and Issue: 33(2), P. 190 - 217

Published: Feb. 13, 2020

Abstract Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but not plants animals who acquire it via the soil their diet, respectively. Animals have evolved highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) humans, signifying its importance, ERG may even status vitamin. accumulates differentially various tissues, according to expression SLC22A4, favouring those such erythrocytes be subject oxidative stress. Mushroom or consumption seems provide significant prevention against stress large systems. strong cytoprotective status, concentration lowered number chronic inflammatory diseases. been passed safe regulatory agencies, value nutraceutical more generally.

Language: Английский

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Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(14), P. 5168 - 5168

Published: July 21, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation thrombosis. Thrombotic thrombotic pathologies are significant accompaniments to lung complications COVID-19. events often occur subjects weak constitutions, multiple risk factors comorbidities. Of particular interest the circulating inflammatory coagulation biomarkers involved directly clotting, specific focus on fibrin(ogen), D-dimer, P-selectin von Willebrand Factor (VWF). Central activity of these their receptors signalling pathways endothelial cells, platelets erythrocytes. In this review, we discuss vascular implications COVID-19 relate biomarker, endothelial, erythrocyte platelet dysfunction. During progression disease, markers be within healthy levels, upregulated eventually depleted. Most patients need treated early progression, when high levels VWF, fibrinogen present, normal slightly increased D-dimer (however, will rapidly increase progresses). Progression VWF depletion even higher followed by cytokine storm, indicative a poor prognosis. We conclude looking at point-of-care devices methodologies management suggest personalized medicine approach should considered treatment patients.

Language: Английский

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The Role of Lipopolysaccharide-Induced Cell Signalling in Chronic Inflammation

Chronic Stress, Journal Year: 2022, Volume and Issue: 6

Published: Jan. 1, 2022

Lipopolysaccharide (LPS) is the main structural component of outer membrane most Gram-negative bacteria and has diverse immunostimulatory procoagulant effects. Even though LPS well described for its role in pathology sepsis, considerable evidence demonstrates that LPS-induced signalling immune dysregulation are also relevant pathophysiology many diseases, characteristically where endotoxaemia less severe. These diseases typically chronic progressive nature span broad classifications, including neurodegenerative, metabolic, cardiovascular diseases. This Review reappraises mechanisms emphasises crucial contribution to multiple beyond conventional sepsis. perspective asserts new ways approaching by targeting LPS-driven pathways may be therapeutic benefit a wide range inflammatory conditions.

Language: Английский

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Long COVID: pathophysiological factors and abnormalities of coagulation

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(6), P. 321 - 344

Published: April 19, 2023

Acute COVID-19 infection is followed by prolonged symptoms in approximately one ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host (chronic inflammation, metabolic endocrine dysregulation, immune autoimmunity); downstream impacts (tissue damage from the initial infection, tissue hypoxia, dysbiosis, autonomic nervous system dysfunction). These mechanisms culminate long-term persistence disorder characterized a thrombotic endothelialitis, endothelial hyperactivated platelets, fibrinaloid microclots. abnormalities blood vessels coagulation affect every organ represent unifying pathway for various

Language: Английский

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Triggers for the onset and recurrence of psoriasis: a review and update

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Psoriasis is an immune-mediated inflammatory skin disease, involving a complex interplay between genetic and environmental factors. Previous studies have demonstrated that factors play major role in the pathogenesis of psoriasis. However, non-genetic are also necessary to trigger onset recurrence psoriasis genetically predisposed individuals, which include infections, microbiota dysbiosis gut, dysregulated lipid metabolism, sex hormones, mental illness. can be induced by other triggers, such as trauma, unhealthy lifestyles, medications. Understanding how these triggers provides insights into pathogenesis, well better clinical administration. In this review, we summarize for update current evidence on underlying mechanism elicit disease.

Language: Английский

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Bacterial Dysbiosis and Translocation in Psoriasis Vulgaris

Frontiers in Cellular and Infection Microbiology, Journal Year: 2019, Volume and Issue: 9

Published: Feb. 4, 2019

Psoriasis vulgaris is a chronic inflammatory skin condition, associated with both physical and psychological burden. Our understanding of the aetiology this disease remains incomplete. Conventionally, psoriasis has been viewed as condition that manifests solely in skin. However, systemic nature confirmed by presence wide array dysregulated cytokines markers serum these patients. Both gut microbiomes have found association psoriasis. An evident also exists between bowel condition. Regarding microbiome, changes observed relative abundance Firmicutes, Actinobacteria Proteobacteria. Additionally, Staphylococcus Streptococcus spp. were detected more frequently lesional Alterations microbiome characterised decrease Bacteroidetes phylum an increase Faecalibacterium genus. We suggest dysbiosis microbiota may contribute to psoriasis, promoting translocation microbes from sites into bloodstream. Consistent Iron Dysregulation Dormant Microbes hypothesis, microorganisms are physiologically dormant state, but be awakened periodically shed their cell wall components, such lipopolysaccharide lipoteichoic acid. inflammagens significantly maintaining state host, seen individuals diagnosed

Language: Английский

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Platelet activity and hypercoagulation in type 2 diabetes

Cardiovascular Diabetology, Journal Year: 2018, Volume and Issue: 17(1)

Published: Nov. 2, 2018

A strong correlation exists between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), with CVD the presence of atherosclerosis being prevailing cause morbidity mortality in diabetic populations. T2DM is accompanied by various coagulopathies, including anomalous clot formation or amyloid fibrin(ogen), dysregulated inflammatory molecules. Platelets are intimately involved thrombus particularly vulnerable to cytokines. The aim this current study was therefore assess whole blood (hyper)coagulability, platelet ultrastructure receptor expression, as well levels IL-1β, IL-6, IL-8 sP-selectin healthy individuals. Platelet morphology assessed through scanning electron microscopy (SEM), while assessment GPIIb/IIIa expression performed confocal flow cytometry addition FITC-PAC-1 CD41-PE antibodies. IL-6 were using a multiplex assay. In there significant upregulation circulating markers, hypercoagulation activation, increased seen microscopy. Analyses showed that these receptors additionally shed onto microparticles, which confirmed SEM. Cumulatively, provides mechanistic evidence pathological states platelets together fibrin(ogen) T2DM, might underpin an risk for events.

Language: Английский

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Parkinson’s Disease: A Systemic Inflammatory Disease Accompanied by Bacterial Inflammagens

Frontiers in Aging Neuroscience, Journal Year: 2019, Volume and Issue: 11

Published: Aug. 27, 2019

Parkinson's disease (PD) is a well-known neurodegenerative with strong association established systemic inflammation. Recently, the role of gingipain protease group from Porphyromonas gingivalis was implicated in Alzheimer's and here we present evidence, using fluorescent antibody to detect R1 (RgpA), its presence PD population. To further elucidate action this gingipain, as well lipopolysaccharide (LPS) P. gingivalis, low concentrations recombinant RgpA LPS were added purified fibrinogen. We also substantiate previous findings regarding by emphasizing inflammation via multiplex cytokine analysis, demonstrate hypercoagulation thromboelastography (TEG), confocal electron microscopy. Biomarker analysis confirmed significantly increased levels circulating proinflammatory cytokines. In our control blood results show hypercoagulation, amyloid formation plasma, profound ultrastructural changes platelets. Our laboratory fibrinogen RgpA, and/or LPS, showed preliminary data regards actions bacterial membrane inflammagen on plasma proteins, better understand nature PD.

Language: Английский

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