scholarly journals Exploring the therapeutic potential of forkhead box O for outfoxing COVID-19

Open Biology ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 210069
Author(s):  
Pradeep Singh Cheema ◽  
Deeptashree Nandi ◽  
Alo Nag
Keyword(s):  
Oxidative Stress ◽  
B Lymphocytes ◽  
Normal Cell ◽  
Therapeutic Potential ◽  
Cell Physiology ◽  
The Novel ◽  
Cytokine Storm ◽  
Forkhead Box ◽  
Foxo Transcription Factors ◽  
Novel Coronavirus

The COVID-19 pandemic has wreaked unprecedented societal havoc worldwide. The infected individuals may present mild to severe symptoms, with nearly 20% of the confirmed patients impaired with significant complications, including multi-organ failure. Acute respiratory distress imposed by SARS-CoV-2 largely results from an aggravated cytokine storm and deregulated immune response. The forkhead box O (FoxO) transcription factors are reported to play a significant role in maintaining normal cell physiology by regulating survival, apoptosis, oxidative stress, development and maturation of T and B lymphocytes, secretion of inflammatory cytokines, etc. We propose a potent anti-inflammatory approach based on activation of the FoxO as an attractive strategy against the novel coronavirus. This regime will be focused on restoring redox and inflammatory homeostasis along with repair of the damaged tissue, activation of lymphocyte effector and memory cells. Repurposing FoxO activators as a means to alleviate the inflammatory burst following SARS-CoV-2 infection can prove immensely valuable in the ongoing pandemic and provide a reliable groundwork for enriching our repertoire of antiviral modalities for any such complication in the future. Altogether, our review highlights the possible efficacy of FoxO activation as a novel arsenal for clinical management of COVID-19.

High cytokine levels and cytokine storm in the novel coronavirus infection

2021 ◽  
pp. 38-47
Author(s):  
Maksim Leonidovich Maksimov ◽  
Albina Ayratovna Zvegintseva ◽  
Lyudmila Yurievna Kulagina ◽  
Albina Zainutdinovna Nigmedzyanova ◽  
Elvina Ramisovna Kadyseva
Keyword(s):  
Peripheral Blood ◽  
High Frequency ◽  
The Novel ◽  
Cytokine Storm ◽  
The Public ◽  
Systemic Inflammatory Reaction ◽  
Scientific World ◽  
Cytokine Levels ◽  
Coronavirus Infection ◽  
Novel Coronavirus

A review article is based on current foreign sources. The level of cytokines in the peripheral blood can be increased in many diseases, but in some cases there may be an excess of their normal concentration in tens, hundreds or more times with the development of a peculiar clinical picture, which is based on a systemic inflammatory reaction. In the literature this condition has received the figurative name «cytokine storm», which highlights an extremely violent reaction of the immune system with an unknown (often unfavorable) outcome. Close attention of the scientific world and the public to the problem of extremely high levels of cytokines in the peripheral blood (hypercytokinemia) was drawn due to the high frequency of the cytokine storm in the novel coronavirus infection.

scholarly journals Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Franck Mauvais-Jarvis ◽  
Sabra L Klein ◽  
Ellis R Levin
Keyword(s):  
Immune Response ◽  
Distress Syndrome ◽  
Immune Dysregulation ◽  
Innate Immune ◽  
The Novel ◽  
Cytokine Storm ◽  
Inflammatory Infiltration ◽  
Biological Sex ◽  
17Β Estradiol ◽  
Novel Coronavirus

Abstract Severe outcomes and death from the novel coronavirus disease 2019 (COVID-19) appear to be characterized by an exaggerated immune response with hypercytokinemia leading to inflammatory infiltration of the lungs and acute respiratory distress syndrome. Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17β-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.

scholarly journals Autophagy Modulation in Lymphocytes From COVID-19 Patients: New Therapeutic Target in SARS-COV-2 Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Marta Vomero ◽  
Cristiana Barbati ◽  
Tania Colasanti ◽  
Alessandra Ida Celia ◽  
Mariangela Speziali ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Degradation Pathway ◽  
The Novel ◽  
Lysosomal Degradation ◽  
Tnf Α ◽  
Evolutionarily Conserved ◽  
Novel Coronavirus ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the “cytokine storm.” Among these, interleukin (IL)-6, tumor necrosis factor‐α (TNF‐α), and IL-1β seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF‐α, and IL-1β in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection.

scholarly journals Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Ziying Wang ◽  
Zhuanli Zhou ◽  
Xinbing Wei ◽  
Mingwei Wang ◽  
Bi-Ou Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
The Novel ◽  
Neuroprotective Effects ◽  
Chemical Structures ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Blood Brain Barrier Integrity

Although studies have seen dramatic advances in the understanding of the pathogenesis of stroke such as oxidative stress, inflammation, excitotoxicity, calcium overload and apoptosis, the delivery of stroke therapies is still a great challenge. In this study, we designed and synthesized a series of novel twin compounds containing tetramethylpyrazine and carnitine substructures and explored their therapeutic potential and mechanism in stroke-related neuronal injury. We first screened the neuroprotective effects of candidate compounds and found that among the tested compounds, LR134 and LR143 exhibited significant neuroprotection as evidenced by reducing cerebral infarct and edema, improving neurological function as well as blood-brain barrier integrity in rats after cerebral ischemia/reperfusion injury. We further demonstrated that the neuroprotective effects of compounds LR134 and LR143 were associated with the reduced inflammatory responses and NADPH oxidase- (NOX2-) mediated oxidative stress and the protection of mitochondria accompanied by the improvement of energy supply. In summary, this study provides direct evidence showing that the novel twin compounds containing tetramethylpyrazine and carnitine substructures have neuroprotective effects with multiple therapeutic targets, suggesting that modulation of these chemical structures may be an innovative therapeutic strategy for treating patients with stroke.

scholarly journals Cytokine Storm in the Novel Coronavirus Infection and Methods of its Correction

2021 ◽  
Vol 65 (11-12) ◽  
pp. 27-37
Author(s):  
A. V. Ershov ◽  
V. D. Surova ◽  
V. T. Dolgikh ◽  
T. I. Dolgikh
Keyword(s):  
Fatal Outcome ◽  
Lung Damage ◽  
The Novel ◽  
Cytokine Storm ◽  
Leading Role ◽  
Average Impact ◽  
Average Impact Factor ◽  
Coronavirus Infection ◽  
Novel Coronavirus

The aim of the study was to identify the role of cytokine storm in COVID-19, that emerged at the end of 2019, based on the analysis of 80 publications, including 17.4% Russian and 82.6% foreign publications for 2014–2020 with an average impact factor of 11.94 and a maximum of 74.699. This review includes an in-depth discussion of the possible causes and pathogenetic factors of cytokine storm syndrome development caused by COVID-19. The results of research on the use of various principles of cytokine storm correction are provided. It has been established that lung damage and the development of a fatal outcome are caused not by the virus itself, but by the hyperreaction of the body's immune system. The leading role in this process belongs to the cytokine storm, including the action of IL-6.

scholarly journals Photosynthetically Controlled Spirulina, but Not Solar Spirulina, Inhibits TNF-α Secretion: Potential Implications for COVID-19-Related Cytokine Storm Therapy

2021 ◽  
Vol 23 (1) ◽  
pp. 149-155
Author(s):  
Asaf Tzachor ◽  
Or Rozen ◽  
Soliman Khatib ◽  
Sophie Jensen ◽  
Dorit Avni
Keyword(s):  
Therapeutic Potential ◽  
Human Subjects ◽  
Arthrospira Platensis ◽  
In Vivo Studies ◽  
Cytokine Storm ◽  
Blue Green Algae ◽  
Tnf Α ◽  
Novel Coronavirus

AbstractAn array of infections, including the novel coronavirus (SARS-CoV-2), trigger macrophage activation syndrome (MAS) and subsequently hypercytokinemia, commonly referred to as a cytokine storm (CS). It is postulated that CS is mainly responsible for critical COVID-19 cases, including acute respiratory distress syndrome (ARDS). Recognizing the therapeutic potential of Spirulina blue-green algae (Arthrospira platensis), in this in vitro stimulation study, LPS-activated macrophages and monocytes were treated with aqueous extracts of Spirulina, cultivated in either natural or controlled light conditions. We report that an extract of photosynthetically controlled Spirulina (LED Spirulina), at a concentration of 0.1 µg/mL, decreases macrophage and monocyte-induced TNF-α secretion levels by over 70% and 40%, respectively. We propose prompt in vivo studies in animal models and human subjects to determine the putative effectiveness of a natural, algae-based treatment for viral CS and ARDS, and explore the potential of a novel anti-TNF-α therapy. Graphical abstract

scholarly journals Cytokine Storm in COVID-19 Patients, their Impact on Organs and the Potential Treatment by QTY Code-Designed Detergent-Free Chemokine Receptors

2020 ◽  
Author(s):  
Mujahed I Mustafa ◽  
Abdelrahman H Abdelmoneim ◽  
Eiman M Mahmoud ◽  
Abdelrafie M Makhawi
Keyword(s):  
Chemokine Receptors ◽  
Protein Modification ◽  
The Body ◽  
The Novel ◽  
Potential Treatment ◽  
Cytokine Storm ◽  
Respiratory Problems ◽  
Human Lungs ◽  
Synthetic Proteins ◽  
Novel Coronavirus

The novel coronavirus in not only causing respiratory problems, it may also damage the heart, kidneys, liver and other organs; in Wuhan 14 to 30% of COVID-19 patients have lost their kidney function and now require either dialysis or kidney transplants. The novel coronavirus gains entry into humans by targeting ACE2 receptor that found on lung cells, which destroy human lungs through cytokine storms, this leads to hyper-inflammation, forcing the immune cells to destroy healthy cells. This is why some COVID-19 patients need intensive care. The inflammatory chemicals released during COVID-19 infection cause the liver to produce proteins that defend the body from infections. However, these proteins can cause blood clotting, which can clog blood vessels in the heart and other organs; as a result, the organs are deprived from oxygen and nutrients which could ultimately lead to multi-organ failure and subsequent progression to acute lung injury, acute respiratory distress syndrome and often death. However, a novel protein modification tool called the QTY code, that are similar in their structure to antibodies, which could provide a solution to excess cytokines, these synthetic proteins can be injected into the body to blind the excess cytokines generated by the cytokine storm; this will eventually remove the excessive cytokines and inhibit the severe symptoms caused by the COVID-19 infection. In this review we will focuses on cytokine storm in COVID-19 patients, their impact on the organs and the potential treatment by QTY code-designed detergent-free chemokine receptors.

FOXO transcription factors: key regulators of cell fate

2006 ◽  
Vol 34 (5) ◽  
pp. 722-726 ◽  
Author(s):  
E.W.-F. Lam ◽  
R.E. Francis ◽  
M. Petkovic
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Transcription Factors ◽  
Cell Fate ◽  
Environmental Cues ◽  
Cellular Functions ◽  
Forkhead Box ◽  
Foxo Transcription Factors ◽  
Stress Damage

FOXO (forkhead box O) transcription factors are crucial regulators of cell fate. This function of FOXO proteins relies on their ability to control diverse and at times, opposing cellular functions, such as proliferation, differentiation, DNA repair, defence against oxidative stress damage and apoptosis, in response to hormones, growth factors and other environmental cues. This review discusses our current understanding of the regulation and role of FOXO transcription factors in determining cell fate and highlights their relevance to tumorigenesis and drug resistance.

scholarly journals Vitamin D regulation of the immune system and its implications for COVID-19: A mini review

2021 ◽  
Vol 9 ◽  
pp. 205031212110140
Author(s):  
Linda Bui ◽  
Zahra Zhu ◽  
Stephanie Hawkins ◽  
Alonso Cortez-Resendiz ◽  
Alfredo Bellon
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Symptoms ◽  
Distress Syndrome ◽  
Clinical Presentation ◽  
Potential Contribution ◽  
The Novel ◽  
Cytokine Storm ◽  
Novel Coronavirus

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is at the origin of the current pandemic, predominantly manifests with severe respiratory symptoms and a heightened immune response. One characteristic of SARS-CoV-2 is its capacity to induce cytokine storm leading to acute respiratory distress syndrome. Consequently, agents with the ability to regulate the immune response, such as vitamin D, could become tools either for the prevention or the attenuation of the most severe consequences of the coronavirus disease 2019 (COVID-19). Vitamin D has shown antimicrobial as well as anti-inflammatory properties. While SARS-CoV-2 promotes the release of proinflammatory cytokines, vitamin D attenuates the release of at least some of these same molecules. Inflammatory cytokines have been associated with the clinical phenomena of COVID-19 and in particular with its most dangerous complications. Therefore, the goals of this article are as follows: first, present the numerous roles vitamin D plays in modulating the immune response; second, gather data currently available on COVID-19 clinical presentation and its relation to cytokines and similar molecules; third, expose what it is known about how coronaviruses elicit an inflammatory reaction; and fourth, discuss the potential contribution of vitamin D in reducing the risk and severity of COVID-19.

scholarly journals Will Remdesivir Reshape Cardiovascular Practice in COVID 19 Era?

2020 ◽  
Author(s):  
A. Mohammed Idhrees ◽  
Prasanna Karthik Suthakaran ◽  
George Jose Valooran ◽  
Mohamad Bashir
Keyword(s):  
Cardiovascular Disease ◽  
Lactate Dehydrogenase ◽  
Clinical Syndrome ◽  
Cardiac Biomarkers ◽  
The Novel ◽  
Cytokine Storm ◽  
Cardiovascular Medicine ◽  
Cardiovascular Comorbidity ◽  
Multiple Organs ◽  
Novel Coronavirus

AbstractInfection with the novel coronavirus, SARS-CoV2, produces the clinical syndrome COVID-19. COVID-19 is a systemic illness inducing hyperinflammation and cytokine storm affecting multiple organs including the myocardium which is reflected in elevated cardiac biomarkers such as troponin, lactate dehydrogenase, and creatinine kinase MB. Furthermore, COVID-19 has been implicated in increased predilection to thromboembolic phenomena. Hence, mortality in patients with associated cardiovascular disease has been higher compared with the cohort with no cardiovascular comorbidity. It is entirely unknown how remdesivir will change the facet of cardiovascular medicine and surgery. In the present constantly changing climate, this review of remdesivir and its association with cardiovascular disease is comprehensive as of June 17, 2020 and it highlights the science behind this drug and its potential implications to cardiovascular practice.

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