scholarly journals Temporal kinetics of RNAemia and associated systemic cytokines in hospitalized COVID-19 patients

2020 ◽  
Author(s):  
Debby van Riel ◽  
Carmen W.E. Embregts ◽  
Gregorius J. Sips ◽  
Johannes P.C. van den Akker ◽  
Henrik Endeman ◽  
...  
Keyword(s):  
Viral Load ◽  
Inflammatory Cytokines ◽  
Severe Disease ◽  
Respiratory Complications ◽  
Viral Spread ◽  
Cytokines And Chemokines ◽  
Wide Range ◽  
Direct Association ◽  
Kinetics Of

SummaryCOVID-19 is associated to a wide range of extra-respiratory complications, of which the pathogenesis is currently not fully understood. In this study we report the temporal kinetics of viral RNA and inflammatory cytokines and chemokines in serum during the course of COVID-19. We show that a RNAemia occurs more frequently and lasts longer in patients that develop critical disease compared to patients that develop moderate or severe disease. Furthermore we show that concentrations of IL-10 and MCP-1—but not IL-6—are associated with viral load in serum. However, higher levels of IL-6 were associated with the development of critical disease. The direct association of inflammatory cytokines with viral load or disease severity highlights the complexity of systemic inflammatory response and the role of systemic viral spread.

Detailed kinetics of hydrogen abstraction from trans-decalin by OH radicals: the role of hindered internal rotation treatment

2020 ◽  
Vol 22 (44) ◽  
pp. 25740-25746
Author(s):  
Tam V.-T. Mai ◽  
Lam K. Huynh
Keyword(s):  
Master Equation ◽  
Hydrogen Abstraction ◽  
Kinetic Mechanism ◽  
Oh Radicals ◽  
Rate Model ◽  
Wide Range ◽  
Detailed Kinetics ◽  
Kinetics Of ◽  
Detailed Kinetic Mechanism

The detailed kinetic mechanism of the trans-decalin + OH reaction is firstly investigated for a wide range of conditions (T = 200–2000 K & P = 0.76–76000 Torr) using the M06-2X/aug-cc-pVTZ level and stochastic RRKM-based Master equation rate model.

scholarly journals Role of some members of chemokine/cytokine network in the pathogenesis of thalassemia and sickle cell hemoglobinopathies: a mini review

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Zahra Mousavi ◽  
Zinat Yazdani ◽  
Alireza Moradabadi ◽  
Fatemeh Hoseinpourkasgari ◽  
Gholamhossein Hassanshahi
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
Cell Disease ◽  
Cytokine Network ◽  
Exact Role ◽  
Cytokines And Chemokines ◽  
Wide Range

Abstract The word of hemoglobinopathy is described for an array of disorders that affecting hemoglobin (Hb) functions. Hb is a molecule with 68 kDa molecular weight, serving as oxygen carrying metalloprotein. Hemoglobinopathy includes a wide range of Hb structural deficits varying from thalassemia to sickle cell disease. Cyto-chemokine network members are pivotally involved in the pathogenesis of hemoglobinopathies, however, the exact role of these mediators in the development of these disorders yet to be well addressed. Cytokines and chemokines are generated by inflamed endothelial cells that promote the expression of their respected receptors and further activate NF-κβ, recruit red blood cells (RBCs) and white blood cells (WBCs) toward the inflamed endothelium. Therefore, due to critical roles played by the cyto-chemokine network in several aspects of hemoglobinopathies pathophysiology including apoptosis of endothelial cells, RBC, WBC and etc.…, in the present review, we focused on the critical parts played by this network in the pathogenesis of hemoglobinopathies.

scholarly journals COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Adèle Lasbleiz ◽  
Bénédicte Gaborit ◽  
Astrid Soghomonian ◽  
Axel Bartoli ◽  
Patricia Ancel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Intensive Care ◽  
Inflammatory Cytokines ◽  
Visceral Adipose Tissue ◽  
Cardiovascular Events ◽  
Low Grade ◽  
Viral Spread ◽  
Visceral Adipose ◽  
Pro Inflammatory Cytokines

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the “cytokine storm” and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

scholarly journals The immune-inflammatory response of oligodendrocytes in a murine model of preterm white matter injury: the role of TLR3 activation

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Marta Boccazzi ◽  
Juliette Van Steenwinckel ◽  
Anne-Laure Schang ◽  
Valérie Faivre ◽  
Tifenn Le Charpentier ◽  
...  
Keyword(s):  
White Matter ◽  
Primary Cultures ◽  
White Matter Injury ◽  
Poly I:C ◽  
Cytokines And Chemokines ◽  
Wide Range ◽  
Preterm Born ◽  
And Function

AbstractA leading cause of preterm birth is the exposure to systemic inflammation (maternal/fetal infection), which leads to neuroinflammation and white matter injury (WMI). A wide range of cytokines and chemokines are expressed and upregulated in oligodendrocytes (OLs) in response to inflammation and numerous reports show that OLs express several receptors for immune related molecules, which enable them to sense inflammation and to react. However, the role of OL immune response in WMI is unclear. Here, we focus our study on toll-like receptor-3 (TLR3) that is activated by double-strand RNA (dsRNA) and promotes neuroinflammation. Despite its importance, its expression and role in OLs remain unclear. We used an in vivo mouse model, which mimics inflammation-mediated WMI of preterm born infants consisting of intraperitoneal injection of IL-1β from P1 to P5. In the IL-1β-treated animals, we observed the upregulation of Tlr3, IL-1β, IFN-β, Ccl2, and Cxcl10 in both PDGFRα+ and O4+ sorted cells. This upregulation was higher in O4+ immature OLs (immOLs) as compared to PDGFRα+ OL precursor cells (OPCs), suggesting a different sensitivity to neuroinflammation. These observations were confirmed in OL primary cultures: cells treated with TLR3 agonist Poly(I:C) during differentiation showed a stronger upregulation of Ccl2 and Cxcl10 compared to cells treated during proliferation and led to decreased expression of myelin genes. Finally, OLs were able to modulate microglia phenotype and function depending on their maturation state as assessed by qPCR using validated markers for immunomodulatory, proinflammatory, and anti-inflammatory phenotypes and by phagocytosis and morphological analysis. These results show that during inflammation the response of OLs can play an autonomous role in blocking their own differentiation: in addition, the immune activation of OLs may play an important role in shaping the response of microglia during inflammation.

scholarly journals Isolation of Skin Leukocytes Uncovers Phagocyte Inflammatory Responses During Induction and Resolution of Cutaneous Inflammation in Fish

2021 ◽  
Vol 12 ◽  
Author(s):  
Amro M. Soliman ◽  
Taekwan Yoon ◽  
Jiahui Wang ◽  
James L. Stafford ◽  
Daniel R. Barreda
Keyword(s):  
Inflammatory Cytokines ◽  
Carassius Auratus ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Skin Infections ◽  
Cutaneous Inflammation ◽  
Pathogen Elimination ◽  
Cytokines And Chemokines ◽  
Kinetics Of ◽  
Pro Inflammatory Cytokines

Leukocytes offer a critical layer of protection to the host following skin infections. Delineating the kinetics of cutaneous leukocyte recruitment as well as their anti-microbial and regulatory profiles is challenging since it requires the isolation of adequate cell numbers and maintenance of their functional properties. Herein, we took advantage of a modified procedure to gain insights into the contributions of fish phagocytes through induction and resolution phases of acute cutaneous inflammation in goldfish (Carassius auratus). Our data shows early upregulation of pro-inflammatory cytokines and chemokines, which was paired with neutrophil-dominant leukocyte migration of neutrophils from circulation to the injury site. Recruited neutrophils were associated with high levels of reactive oxygen species (ROS). Following pathogen elimination, a reduction in ROS levels and pro-inflammatory cytokines expression preceded the resolution of inflammation. These results provide a better understanding of the cutaneous immune responses in fish. Moreover, the increased viability and functionality of isolated skin leukocytes opens the door to better understand a range of additional skin diseases.

Characteristic pro-inflammatory cytokines and host defence cathelicidin peptide produced by human monocyte-derived macrophages infected withNeospora caninum

Parasitology ◽  
2017 ◽  
Vol 145 (7) ◽  
pp. 871-884 ◽  
Author(s):  
E. Boucher ◽  
M. Marin ◽  
R. Holani ◽  
M. Young-Speirs ◽  
D.M. Moore ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Cell Model ◽  
Neospora Caninum ◽  
Severe Disease ◽  
Human Monocyte ◽  
Host Defence ◽  
Mitogen Activated Protein Kinase ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Pro Inflammatory Cytokines

AbstractNeospora caninumis a coccidian intracellular protozoan capable of infecting a wide range of mammals, although severe disease is mostly reported in dogs and cattle. Innate defences triggered by monocytes/macrophages are key in the pathogenesis of neosporosis, as these cells are first-line defenders against intracellular infections. The aim of this study was to characterize infection and innate responses in macrophages infected withN. caninumusing a well-known cell model to study macrophage functions (human monocyte THP-1 cells). Intracellular invasion of live tachyzoites occurred as fast as 4 h (confirmed with immunofluorescence microscopy usingN. caninum-specific antibodies). Macrophages infected byN. caninumhad increased expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-8, IFNγ). Interestingly,N. caninuminduced expression of host-defence peptides (cathelicidins), a mechanism of defence never reported forN. caninuminfection in macrophages. The expression of cytokines and cathelicidins in macrophages invaded byN. caninumwas mediated by mitogen-activated protein kinase (MEK 1/2). Secretion of such innate factors fromN. caninum-infected macrophages reduced parasite internalization and promoted the secretion of pro-inflammatory cytokines in naïve macrophages. We concluded that rapid invasion of macrophages byN. caninumtriggered protective innate defence mechanisms against intracellular pathogens.

scholarly journals Inflammatory mechanisms of mental illness: brain inflammatory response to interferon stimulation

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S256-S256
Author(s):  
James Herron ◽  
Jonathan Cavanagh
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Significant Risk ◽  
Sickness Behaviour ◽  
Immune Mechanisms ◽  
Cytokines And Chemokines ◽  
The Brain

AimsWe hypothesise that peripheral IFN stimulation results in a brain inflammatory response via pathways of neuroimmune communication which in turn results in sickness-behaviour and depressive phenotype. We aim to determine if peripheral IFN stimulation results in brain inflammatory response including upregulation of inflammatory cytokines and chemokines.BackgroundThere is increasing interest in the role of dysregulated immune function and inflammation in the pathogenesis of psychiatric disorders including mood disorders and dementias. Immune mechanisms offer a new approach to investigating mechanism in addition to offering hope for new avenues of treatment.Interferon (IFN) therapy in humans is known to be associated with a significant risk of developing depression, both during therapy and increasing risk of relapse in the years following exposure, yet the mechanism remains unclear. IFN stimulation in animal models may offer insights into this phenomenon, in addition to furthering our understanding the role of immune mechanisms in the development of psychiatric phenotypes.MethodMice (n. 42) were exposed to either IFN-alpha, IFN-gamma or vehicle control using either osmotic pump or intraperitoneal injection over the course of 7 days. Mice were scarificed, brains were dissected and RNA extracted. Inflammatory gene transcription within the brain was determined using real time quantitative polymerase chain reaction (RTqPCR). Absolute quantification was achieved using standard curves and reference gene. Statistical significance was determined using Mann-Whitney or ANOVA/Kruskal-Wallis depending on normality of data and number of groups.ResultIFNγ stimulation is associated with a significant brain upregulation of a number of inflammatory cytokines and chemokines including Il1β, Tnfα, Il10, Ifnγ, Ccl2, Ccl5, Ccl19, Cxcl10 and Ccr5. However, unexpectedly we did not find IFNα stimulation to associate with brain inflammatory transcriptional changes.ConclusionThis work demonstrates a brain inflammatory response to peripheral IFNγ stimulation. The inflammatory profile, including upregulated chemokines, suggests that recruitment of leukocytes across the blood brain barrier may be part of the immune response. Further experiments using existing tissues will explore if there are structural/cellular changes within the brain parenchyma. Further experiments within the group will seek to demonstrate if IFN treatment associates with sickness behaviour in order to determine if this is a clinically meaningful model. Suprisingly, we did not see similar changes in the IFNα treated group, which requires further investigation.Funding: University of Glasgow, The Sackler Trust

scholarly journals Impact of Viral Decontamination Method on Cytokine Profile of COVID-19 Patients

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1287
Author(s):  
Davide Magrì ◽  
Anna Navarro ◽  
Federica Bergami ◽  
Elena Percivalle ◽  
Alessandro Ferrari ◽  
...  
Keyword(s):  
Viral Load ◽  
Complete Removal ◽  
High Viral Load ◽  
Reliable Data ◽  
Sample Processing ◽  
Special Equipment ◽  
Cytokines And Chemokines ◽  
Load Removal ◽  
Ultraviolet C

COVID-19 related morbidity and mortality have been often attributed to an exaggerated immune response. The role of cytokines and chemokines in COVID-19 and their contributions to illness severity are known, and thus their profiling from patient bronchoalveolar lavage (BAL) samples would help in understanding the disease progression. To date, limited studies have been performed on COVID-19 BAL samples, as the manipulation of such specimens (potentially containing live viruses) requires several laboratorial precautions, such as personnel training and special equipment, a requirement that not all laboratories can fulfil. Here, we assessed two fast and easily applicable methods (ultrafiltration and ultraviolet–C irradiation) for their impact on viral load removal or inactivation, respectively and on cytokine profiles preservation. Eight samples of BAL fluids from SARS-CoV2 patients with high viral load were tested. For both methods, complete removal was confirmed by lack of viral replication in Vero E6 cells and by RT-qPCR. Although both methods showed to remove completely the active SARS-CoV2 viral load, only UVC treatment has little or no quantitative effect on total cytokines/chemokines measurements, however cytokines profile and relative ratios are preserved or minimally altered when compared data obtained by the two different decontamination methods. Sample preparation and manipulation can greatly affect the analytical results; therefore, understanding if changes occurred after sample processing is of outmost importance for reliable data and can be useful to improve clinical practice.

scholarly journals Versatile Role of Prokineticins and Prokineticin Receptors in Neuroinflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1648
Author(s):  
Roberta Lattanzi ◽  
Rossella Miele
Keyword(s):  
Inflammatory Cytokines ◽  
Adaptive Responses ◽  
New Class ◽  
Prokineticin 2 ◽  
Wide Range ◽  
Gastrointestinal Inflammation ◽  
Low Levels ◽  
Inflammatory Component ◽  
Pro Inflammatory Cytokines

Prokineticins are a new class of chemokine-like peptides involved in a wide range of biological and pathological activities. In particular, prokineticin 2 (PK2), prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) play a central role in modulating neuroinflammatory processes. PK2 and PKRs, which are physiologically expressed at very low levels, are strongly upregulated during inflammation and regulate neuronal-glial interaction. PKR2 is mainly overexpressed in neurons, whereas PKR1 and PK2 are mainly overexpressed in astrocytes. Once PK2 is released in inflamed tissue, it is involved in both innate and adaptive responses: it triggers macrophage recruitment, production of pro-inflammatory cytokines, and reduction of anti-inflammatory cytokines. Moreover, it modulates the function of T cells through the activation of PKR1 and directs them towards a pro-inflammatory Th1 phenotype. Since the prokineticin system appears to be upregulated following a series of pathological insults leading to neuroinflammation, we will focus here on the involvement of PK2 and PKRs in those pathologies that have a strong underlying inflammatory component, such as: inflammatory and neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, obesity, diabetes, and gastrointestinal inflammation.

scholarly journals Lifetime of actin-dependent protein nanoclusters

2022 ◽  
Author(s):  
Sumantra Sarkar ◽  
Debanjan Goswami
Keyword(s):  
Spatial Organization ◽  
Lipid Membrane ◽  
Simple Extension ◽  
Ligand Interaction ◽  
Cellular Processes ◽  
Wide Range ◽  
Dependent Protein ◽  
Protein Ligand Interaction ◽  
Kinetics Of

Protein nanoclusters (PNCs) are dynamic collections of a few proteins that spatially organize in nanometer length clusters. PNCs are one of the principal forms of spatial organization of membrane proteins and they have been shown or hypothesized to be important in various cellular processes, including cell signaling. PNCs show remarkable diversity in size, shape, and lifetime. In particular, the lifetime of PNCs can vary over a wide range of timescales. The diversity in size and shape can be explained by the interaction of the clustering proteins with the actin cytoskeleton or the lipid membrane, but very little is known about the processes that determine the lifetime of the nanoclusters. In this paper, using mathematical modelling of the cluster dynamics, we model the biophysical processes that determine the lifetime of actin-dependent PNCs. In particular, we investigated the role of actin aster fragmentation, which had been suggested to be a key determinant of the PNC lifetime, and found that it is important only for a small class of PNCs. A simple extension of our model allowed us to investigate the kinetics of protein-ligand interaction near PNCs. We found an anomalous increase in the lifetime of ligands near PNCs, which agrees remarkably well with experimental data on RAS-RAF kinetics. In particular, analysis of the RAS-RAF data through our model provides falsifiable predictions and novel hypotheses that will not only shed light on the role of RAS-RAF kinetics in various cancers, but also will be useful in studying membrane protein clustering in general.

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