Immunotherapy Summary for Cytokine Storm in COVID-19

COVID-19 pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ravaged the world, resulting in an alarming number of infections and deaths, and the number continues to increase. The pathogenesis caused by the novel coronavirus was found to be a disruption of the pro-inflammatory/anti-inflammatory response. Due to the lack of effective treatments, different strategies and treatment methods are still being researched, with the use of vaccines to make the body immune becoming the most effective means of prevention. Antiviral drugs and respiratory support are often used clinically as needed, but are not yet sufficient to alleviate the cytokine storm (CS) and systemic inflammatory response syndrome. How to neutralize the cytokine storm and inhibit excessive immune cell activation becomes the key to treating neocoronavirus pneumonia. Immunotherapy through the application of hormones and monoclonal antibodies can alleviate the immune imbalance, but the clinical effectiveness and side effects remain controversial. This article reviews the pathogenesis of neocoronavirus pneumonia and discusses the immunomodulatory therapies currently applied to COVID-19. We aim to give some conceptual thought to the prevention and immunotherapy of neocoronavirus pneumonia.

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A bi-directional dialog between vascular cells and monocytes/macrophages regulates tumor progression

Cancer and Metastasis Reviews ◽

10.1007/s10555-021-09958-2 ◽

2021 ◽

Author(s):

Victor Delprat ◽

Carine Michiels

Keyword(s):

Tumor Progression ◽

Cancer Progression ◽

Cell Activation ◽

Molecular Mechanisms ◽

Immune Cell ◽

The Body ◽

Vascular Cells ◽

Tumor Associated Macrophage ◽

Immune Cell Activation ◽

The Impact

AbstractCancer progression largely depends on tumor blood vessels as well on immune cell infiltration. In various tumors, vascular cells, namely endothelial cells (ECs) and pericytes, strongly regulate leukocyte infiltration into tumors and immune cell activation, hence the immune response to cancers. Recently, a lot of compelling studies unraveled the molecular mechanisms by which tumor vascular cells regulate monocyte and tumor-associated macrophage (TAM) recruitment and phenotype, and consequently tumor progression. Reciprocally, TAMs and monocytes strongly modulate tumor blood vessel and tumor lymphatic vessel formation by exerting pro-angiogenic and lymphangiogenic effects, respectively. Finally, the interaction between monocytes/TAMs and vascular cells is also impacting several steps of the spread of cancer cells throughout the body, a process called metastasis. In this review, the impact of the bi-directional dialog between blood vascular cells and monocytes/TAMs in the regulation of tumor progression is discussed. All together, these data led to the design of combinations of anti-angiogenic and immunotherapy targeting TAMs/monocyte whose effects are briefly discussed in the last part of this review.

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Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201400761 ◽

2015 ◽

Vol 59 (5) ◽

pp. 991-999 ◽

Cited By ~ 82

Author(s):

Carmen P. Wong ◽

Nicole A. Rinaldi ◽

Emily Ho

Keyword(s):

Inflammatory Response ◽

Zinc Deficiency ◽

Cell Activation ◽

Immune Cell ◽

Immune Cell Activation

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The Flavonoid Fisetin Attenuates Postischemic Immune Cell Infiltration, Activation and Infarct Size after Transient Cerebral Middle Artery Occlusion in Mice

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.189 ◽

2012 ◽

Vol 32 (5) ◽

pp. 835-843 ◽

Cited By ~ 63

Author(s):

Mathias Gelderblom ◽

Frank Leypoldt ◽

Jan Lewerenz ◽

Gabriel Birkenmayer ◽

Denise Orozco ◽

...

Keyword(s):

Inflammatory Response ◽

Infarct Size ◽

Brain Tissue ◽

Tissue Damage ◽

Cell Activation ◽

Immune Cell ◽

Biological Effects ◽

Artery Occlusion ◽

Immune Cell Activation

The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor α (TNFα) production. Fisetin also inhibited LPS-induced TNFα production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor κB activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia.

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Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis

Current Medicinal Chemistry ◽

10.2174/09298673113209990162 ◽

2013 ◽

Vol 20 (37) ◽

pp. 4806-4814 ◽

Cited By ~ 8

Author(s):

Brigitta Buttari ◽

Elisabetta Profumo ◽

Rita Businaro ◽

Luciano Saso ◽

Raffaele Capoano ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Cell Activation ◽

Immune Cell ◽

Therapeutic Targets ◽

Immune Cell Activation ◽

Novel Therapeutic

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Neuronal guidance proteins in cardiovascular inflammation

Basic Research in Cardiology ◽

10.1007/s00395-021-00847-x ◽

2021 ◽

Vol 116 (1) ◽

Author(s):

Marius Keller ◽

Valbona Mirakaj ◽

Michael Koeppen ◽

Peter Rosenberger

Keyword(s):

Cell Activation ◽

Immune Cell ◽

Vascular Endothelial ◽

Therapeutic Approaches ◽

Immune Cell Activation ◽

Cytokines And Chemokines ◽

The Future ◽

Cardiovascular Pathologies ◽

Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

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Oxidative stress and immune cell activation quantification in sepsis and non-sepsis critical care patients by neopterin/7,8-dihydroneopterin analysis

Pteridines ◽

10.1515/pteridines-2020-0015 ◽

2020 ◽

Vol 31 (1) ◽

pp. 68-82

Author(s):

Gregory Baxter-Parker ◽

Ravinder Reddy Gaddam ◽

Elena Moltchanova ◽

Anitra Carr ◽

Geoff Shaw ◽

...

Keyword(s):

Oxidative Stress ◽

Kidney Function ◽

Cell Activation ◽

Immune Cell ◽

Intensive Care Patients ◽

Immune Cell Activation ◽

Immune System Activation ◽

System Activation ◽

Urinary Neopterin ◽

Critical Care Patients

AbstractIntroduction: Neopterin and 7,8-dihydroneopterin are used as biomarkers of oxidative stress and inflammation, but the effect of kidney function on these measurements has not been extensively explored. We examine the levels of oxidative stress, inflammation and kidney function in intensive patients and compare them to equivalent patients without sepsis.Methods: 34 Intensive care patients were selected for the study, 14 without sepsis and 20 with. Both groups had equivalent levels of trauma, assessed by SAPS II, SOFA, and APACHE II and III scores. Plasma and urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) values were measured.Results: Neopterin and total neopterin were significantly elevated in urine and plasma for multiple days in sepsis versus non-sepsis patients. Plasma neopterin and total neopterin have decreasing relationships with increased eGFR (p<0.008 and p<0.001, respectively). Plasma/urinary neopterin and total neopterin ratios demonstrate that total neopterin flux is more influenced by eGFR than neopterin, with significantce of p<0.02 and p<0.0002 respectively.Conclusion: Sepsis patients present with greater levels of oxidative stress and immune system activation than non-sepsis patients of equal levels of trauma, as measured by neopterin and total neopterin. eGFR may need to be taken into account when accessing the level of inflammation from urinary neopterin measurements.

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RhoA Signaling in Immune Cell Response and Cardiac Disease

Cells ◽

10.3390/cells10071681 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1681

Author(s):

Lucia Sophie Kilian ◽

Derk Frank ◽

Ashraf Yusuf Rangrez

Keyword(s):

Cardiac Disease ◽

Cell Response ◽

Cell Activation ◽

Immune Cell ◽

Inflammatory Diseases ◽

Heart Diseases ◽

Small Gtpase ◽

Cardiac Inflammation ◽

Immune Cell Activation ◽

Immune Cell Response

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spiral down to immune cell activation and chronic state of low-level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

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Hybrid Nanoassemblies from Viruses and DNA Nanostructures

Nanomaterials ◽

10.3390/nano11061413 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1413

Author(s):

Sofia Ojasalo ◽

Petteri Piskunen ◽

Boxuan Shen ◽

Mauri A. Kostiainen ◽

Veikko Linko

Keyword(s):

Cell Activation ◽

Immune Cell ◽

Dna Nanotechnology ◽

Biological Properties ◽

Dna Nanostructures ◽

Dna Structures ◽

Nanoscale Structures ◽

Immune Cell Activation ◽

Wide Range ◽

Structural Dna Nanotechnology

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.

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