PathoBiochemistry-directed Guidelines for COVID-19

Patients with underlying health conditions are at risk for a poor outcome from Coronavirus disease 2019 (COVID-19). Using machine reasoning by the sci.AI system, we investigated the pathobiochemistry of this observation to generate therapeutic guidelines. Facts were extracted and linked from publications available in nlm.nih.gov and Europe PMC to form the dataset which was validated by medical experts. Previously we described how preexisting chronic inflammation renders the acute inflammatory response to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) excessive translating the SARS-CoV-2 infection into the clinical COVID-19 syndrome. Herein we focus on therapeutic interventions that mitigate the immune response. In essence, from bench to bedside, as depicted in the Graphical Abstract, the clinical management of COVID-19 should aim at: A. Control of excessive oxidant production. B. Neutralization of excessive oxidants. C. Upregulation of nitric oxide (NO) production.

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Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

Scientific Reports ◽

10.1038/s41598-020-80804-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Haidy A. Saleh ◽

Eman Ramdan ◽

Mohey M. Elmazar ◽

Hassan M. E. Azzazy ◽

Anwar Abdelnaser

Keyword(s):

Nitric Oxide ◽

Inflammatory Response ◽

Raw 264.7 Cells ◽

Inos Mrna ◽

No Production ◽

Raw 264.7 ◽

Mrna Levels ◽

Protective Effects ◽

Tnf Α ◽

Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

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Acute inflammation and hematological response in Nile tilapia fed supplemented diet with natural extracts of propolis and Aloe barbadensis

Brazilian Journal of Biology ◽

10.1590/1519-6984.02413 ◽

2015 ◽

Vol 75 (2) ◽

pp. 491-496 ◽

Cited By ~ 5

Author(s):

G. Dotta ◽

J. Ledic-Neto ◽

ELT. Gonçalves ◽

A. Brum ◽

M. Maraschin ◽

...

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Nile Tilapia ◽

Acute Inflammation ◽

Leukocyte Count ◽

Acute Inflammatory Response ◽

Swim Bladder ◽

Aloe Barbadensis ◽

Natural Extracts ◽

Number Of Cells

This study evaluated the acute inflammatory response induced by carrageenin in the swim bladder of Nile tilapia supplemented with the mixture of natural extracts of propolis and Aloe barbadensis (1:1) at a concentration of 0.5%, 1% and 2% in diet during 15 days. Thirty-six fish were distributed into four treatments with three replicates: fish supplemented with 0.5% of admix of extracts of propolis and Aloe (1:1) injected with 500 µg carrageenin; fish supplemented with 1% of admix of extracts of propolis and Aloe (1:1) injected with 500 µg carrageenin; fish supplemented with 2% of admix of extracts of propolis and Aloe (1:1), injected with 500 µg carrageenin and unsupplemented fish injected with 500 µg carrageenin. Six hours after injection, samples of blood and exudate from the swim bladder of fish were collected. It was observed an increase in the leukocyte count in the swim bladder exudate of fish supplemented with extracts of propolis and Aloe injected with carrageenin. The most frequent cells were macrophages followed by granular leukocytes, thrombocytes and lymphocytes. Supplementation with propolis and Aloe to 0.5% caused a significant increase in the number of cells on the inflammatory focus mainly macrophages, cells responsible for the phagocytic activity in tissues, agent of innate fish immune response.

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Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected withParacoccidioides brasiliensis

Mediators of Inflammation ◽

10.1155/2016/3183285 ◽

2016 ◽

Vol 2016 ◽

pp. 1-17 ◽

Cited By ~ 9

Author(s):

Paula Andrea Pino-Tamayo ◽

Juan David Puerta-Arias ◽

Damaris Lopera ◽

Martha Eugenia Urán-Jiménez ◽

Ángel González

Keyword(s):

Monoclonal Antibody ◽

Immune Response ◽

Inflammatory Response ◽

Paracoccidioides Brasiliensis ◽

Yeast Cells ◽

Histopathological Analysis ◽

Acute Inflammatory Response ◽

Fungal Load ◽

Inflammatory Immune Response

Neutrophils predominate during the acute phase of theParacoccidioides brasiliensisinfection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with1.5×106or2×106P. brasiliensisyeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with1.5×106yeast cells died during the first two weeks after infection. When mice were treated and infected with2×106yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γand IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis.

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SARS-CoV-2 induces inflammasome-dependent pyroptosis and downmodulation of HLA-DR in human monocytes

10.1101/2020.08.25.20182055 ◽

2020 ◽

Author(s):

André C. Ferreira ◽

Vinicius Cardoso Soares ◽

Isaclaudia G. de Azevedo-Quintanilha ◽

Suelen da Silva Gomes Dias ◽

Natalia Fintelman-Rodrigues ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Severe Acute Respiratory Syndrome ◽

Inflammatory Response ◽

Inflammatory Cell ◽

Viral Infections ◽

Relevant Information ◽

Inflammasome Activation ◽

Human Monocytes ◽

Hla Dr

AbstractInfection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocyte death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with COVID-19. Here, we show that SARS-CoV-2 induces inflammasome activation and cell death by pyroptosis in human monocytes, experimentally infected and from patients under intensive care. Pyroptosis was dependent on caspase-1 engagement, prior to IL-1ß production and inflammatory cell death. Monocytes exposed to SARS-CoV-2 downregulate HLA-DR, suggesting a potential limitation to orchestrate the immune response. Our results originally describe mechanisms by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb to control severe 2019 coronavirus disease (COVID-19).Author summarySince its emergence in China in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide. Currently, the number of individuals infected with SARS-CoV-2 and in need of antiviral, anti-inflammatory, anticoagulant and more invasive treatments has overwhelmed the health systems worldwide. In our study, we found that SARS-CoV-2 is capable of inducing inflammatory cell death in human monocytes, one of the main cell types responsible for anti-SARS-CoV-2 immune response. As a consequence of this intracellular inflammatory mechanism (inflammasome engagement), an exacerbated production of inflammatory mediators occurs. The infection also decreases the expression of HLA-DR in monocytes, a molecule related to the orchestration of the immune response in case of viral infections. We also demonstrated that the HIV-1 protease inhibitor, atazanavir (ATV), prevented the uncontrolled inflammatory response, cell death and reduction in HLA-DR expression in SARS-CoV-2-infected monocytes. Our study provides relevant information on the effects of SARS-CoV-2 infection on human monocytes, as well as on the effect of ATV in preventing these pathological effects on the host.

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Forsythiaside attenuates Escherichia coli lipopolysaccharide-induced liver acute inflammatory response in chicken

European Journal of Inflammation ◽

10.1177/2058739219826793 ◽

2019 ◽

Vol 17 ◽

pp. 205873921982679 ◽

Cited By ~ 1

Author(s):

Jingwen Bai ◽

Xiaoting Wang ◽

Meiqi Hao ◽

He Li ◽

Guangdong Cheng ◽

...

Keyword(s):

Nitric Oxide ◽

Escherichia Coli ◽

Inflammatory Response ◽

Mrna Expression ◽

Control Group ◽

Interleukin 17 ◽

Acute Inflammatory Response ◽

Total Proteins ◽

Necrosis Factor Alpha ◽

Escherichia Coli Lipopolysaccharide

This study investigated the effects of forsythiaside on the acute inflammatory response induced by Escherichia coli lipopolysaccharide (LPS) in liver of broiler chickens. Fifteen-day-old chickens were randomly assigned to three groups (n = 20 for each group, orally treated with 0, 30, or 60 mg/kg BW of forsythiaside) for 7 days. At 21 days of age, the chickens were intravenously injected with either LPS (200 μg/kg BW) or sterile saline (200 μg/kg BW, control group). All the chickens were humanely euthanized by cervical dislocation 2 h after the LPS injection. The results showed that the injection of LPS induced some indexes, including total proteins, nitric oxide (NO), interleukin-1beta (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) production ( P < 0.05) and increased the mRNA expression of LPS-induced tumor necrosis factor-alpha (LITAF), IL-1β, IL-17, IL-6, and inducible nitric oxide synthase (iNOS) ( P < 0.05). Forsythiaside supplementation alleviated the LPS-induced inflammatory response by inhibiting the production of total proteins, NO, LITAF, IL-1β, IL-17, and IL-6 and down-regulating the mRNA expression of pro-inflammatory cytokines and iNOS. In conclusion, forsythiaside is a potential treatment for LPS-induced liver acute inflammation in chicken.

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Pleiotropic effects of Nitric Oxide on SARS-CoV-2 Infections

Coronaviruses ◽

10.2174/2666796701999201230121515 ◽

2020 ◽

Vol 01 ◽

Author(s):

Barbara Terroni ◽

Juliana Romano Lopes ◽

Chung Man Chin ◽

Jean Leandro Dos Santos

Keyword(s):

Nitric Oxide ◽

Immune Response ◽

Vascular Endothelium ◽

Cellular Adhesion ◽

Therapeutic Interventions ◽

Vascular Injuries ◽

Prothrombotic State ◽

Inflammatory State ◽

Endothelial Cell Death ◽

Low Levels

: Infection by the β -coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) alters the homeostasis of the vascular endothelium, promoting an inflammatory state which is causes damage and favors the prothrombotic state. The direct viral cytotoxicity induced by the SARS-CoV-2 leads to endothelial cell death; thus, altering the vessel functions. Moreover, SARS-CoV infection induces endothelial dysfunction (ED) and reduces the levels of nitric oxide (NO); thus, aggravating the vascular injuries, which promotes thrombotic events due to an alteration in the homeostasis. NO is a pleiotropic molecule that induces vasodilation, regulates the immune response, inhibits platelet aggregation, and decreases the cellular adhesion to vascular endothelium. Moreover, NO acts directly against invasive agents, exhibiting antibacterial, antiviral, and antifungal activity. Low levels of NO result in an increase in the ED, causing an inflammatory amplification that aggravates the disease through undesirable positive feedback. The objective of this review was to present and discuss the involvement of NO on ED in SARS-CoV-2 infections. This review may also highlight new perspectives for therapeutic interventions through the supplementation of exogenous NO. The maintenance of homeostatic NO levels could represent a useful approach in the prevention of coronavirus-induced ED.

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Hyperinflammation and Immune Response Generation in COVID-19

NeuroImmunoModulation ◽

10.1159/000513198 ◽

2020 ◽

pp. 1-7

Author(s):

Kamla Prasad Mishra ◽

Ajay Kumar Singh ◽

Shashi Bala Singh

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Inflammatory Response ◽

Disease Severity ◽

Human Body ◽

Scientific Community ◽

The Other ◽

Complement Proteins ◽

Cytokines And Chemokines ◽

Cell Mediated Immune Response

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. The pathophysiology of this virus is not very clearly known, thus, enormous efforts are being made by the scientific community to delineate its evading mechanism. In this review, we have summarized the hyperinflammation and humoral and cell-mediated immune response generated in human body after infection with the SARS-CoV-2 virus. The inflammatory response generated after infection by increased proinflammatory cytokines and chemokines, and complement proteins activation may likely contribute to disease severity. We also discussed the other factors that may affect immunity and could be important comorbidities in the disease severity and outcome.

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RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes

Cell Death and Disease ◽

10.1038/s41419-021-04012-z ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Yuting Meng ◽

Qiong Zhang ◽

Kaihang Wang ◽

Xujun Zhang ◽

Rongwei Yang ◽

...

Keyword(s):

Immune Response ◽

Cell Death ◽

Severe Acute Respiratory Syndrome ◽

Programmed Cell Death ◽

Inflammatory Response ◽

Disease Severity ◽

Biological Processes ◽

Underlying Mechanisms ◽

Microarray Analyses

AbstractSevere coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize the m6A epitranscriptome. The results revealed distinct global m6A profiles in severe and mild COVID-19 patients. Programmed cell death and inflammatory response were the major biological processes modulated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, RBM15, a major m6A methyltransferase, was significantly elevated and positively correlated with disease severity. Silencing RBM15 drastically reduced lymphocyte death in vitro. Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. This study shows that SARS-CoV-2 infection alters the m6A epitranscriptome of lymphocytes, particularly in the case of severe patients. RBM15 regulated host immune response to SARS-CoV-2 by elevating m6A modifications of multitarget genes. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.

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Analysis of the immune response in padel

Fizicko vaspitanje i sport kroz vekove ◽

10.5937/spes2102134c ◽

2021 ◽

Vol 8 (2) ◽

pp. 134-140

Author(s):

Cádiz Pía ◽

Carlos Otín ◽

Luis Páez ◽

la de

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Physiological Response ◽

Acute Inflammatory Response ◽

General State ◽

Sports Performance ◽

Before And After ◽

Anti Inflammatory ◽

High Level ◽

Sports Activities

High intensity exercise and sports activities are closely related to a general state of inflammation that can lead to immunosuppression. This physiological response could decrease sports performance and even compromise the athlete's health. The objective of this study was to investigate the acute inflammatory response of a padel match. 15 elite players (28.2±7.9 years) participated voluntarily in the study. Different pro-inflammatory (IL-1ß, IL-2, IL-6, IL-7, IL-8, IL-12 and TNFa) and anti-inflammatory cytokines (IL-5, IL-10 and IL-13) were analyzed before and after a match. The results showed a decrease in IL-7 (p=0.007) and IL-8 (p<0.03) and increases in IL-10 (p<0.04). The results obtained suggest that the practice of high-level padel induces an anti-inflammatory response.

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Enhanced immune response by vacuoles isolated from Saccharomyces cerevisiae in RAW 264.7 macrophages

Bioscience Reports ◽

10.1042/bsr20211158 ◽

2021 ◽

Vol 41 (9) ◽

Author(s):

Su-Min Lee ◽

Wooil Choi ◽

Woo-Ri Shin ◽

Yang-Hoon Kim ◽

Jiho Min

Keyword(s):

Nitric Oxide ◽

Saccharomyces Cerevisiae ◽

Immune Response ◽

Inflammatory Cytokines ◽

Membrane Vesicles ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Abstract Vacuoles are membrane vesicles in eukaryotic cells, the digestive system of cells that break down substances absorbed outside the cell and digest the useless components of the cell itself. Researches on anticancer and intractable diseases using vacuoles are being actively conducted. The practical application of the present study to animals requires the determination of the biocompatibility of vacuole. In the present study, we evaluated the effects of vacuoles isolated from Saccharomyces cerevisiae in RAW 264.7 cells. This showed a significant increase in the production of nitric oxide (NO) produced by macrophage activity. Using Reactive Oxygen Species (ROS) assay, we identified that ROS is increased in a manner dependent on vacuole concentration. Western blot analysis showed that vacuole concentration-dependently increased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). Therefore, iNOS expression was stimulated to induce NO production. In addition, pro-inflammatory cytokines levels promoted, such as interleukin (IL) 6 (IL-6) and tumor necrosis factor (TNF) α (TNF-α). In summary, vacuoles activate the immune response of macrophages by promoting the production of immune-mediated transporters NO, ROS, and pro-inflammatory cytokines.

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