scholarly journals Protective Effect of Arbidol Against Pulmonary Fibrosis and Sepsis in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Hailong Li ◽  
Rui Liu ◽  
Ruotong Zhang ◽  
Shanshan Zhang ◽  
Yiying Wei ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Antiviral Drug ◽  
Dynamic Compliance ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Cytokine Storm ◽  
Viral Immunology ◽  
Sepsis Induction ◽  
Sepsis Score

From the perspective of epidemiology, viral immunology and current clinical research, pulmonary fibrosis may become one of the complications of patients with Coronavirus Disease 2019 (COVID-19). Cytokine storm is a major cause of new coronavirus death. The purpose of this study was to explore the effects of antiviral drug arbidol on cytokine storm and pulmonary fibrosis. Here, we use a mouse model of bleomycin-induced pulmonary fibrosis and a mouse model of fecal dilution-induced sepsis to evaluate the effects of arbidol on pulmonary fibrosis and cytokine storm. The results showed that arbidol significantly reduced the area of pulmonary fibrosis and improved lung function (reduced inspiratory resistance, lung dynamic compliance and forced vital capacity increased). Treatment with arbidol promoted reduced sepsis severity 48 h after sepsis induction, based on weight, murine sepsis score and survival rate. Arbidol observably alleviates inflammatory infiltrates and injury in the lungs and liver. Finally, we also found that arbidol reduced serum levels of pro-inflammatory factors such as TNF-α and IL-6 induced by fecal dilution. In conclusion, our results indicate that arbidol can alleviate the severity of pulmonary fibrosis and sepsis, and provide some reference for the treatment of cytokine storm and sequelae of pulmonary fibrosis in patients with COVID-19.

scholarly journals Both Baicalein and Gallocatechin Gallate Efficaciously Inhibit SARS-CoV-2 Replication by Targeting Mpro and Sepsis in Mice

2021 ◽  
Author(s):  
Ting Xiao ◽  
Mengqi Cui ◽  
Caijuan Zheng ◽  
Peipei Zhang ◽  
Shanfa Ren ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antiviral Drug ◽  
Case Fatality ◽  
Symptomatic Treatment ◽  
Inflammatory Factors ◽  
Cytokine Storm ◽  
Global Pandemic ◽  
Sepsis Score ◽  
Gallocatechin Gallate ◽  
Novel Coronavirus

Abstract Severe acute syndrome coronavirus 2(SARS-CoV-2) caused the global pandemic of COVID-19 since December 2019. Although most of COVID-19’s patients are mild or common, most of the severe patients have sepsis caused by the cytokine storm, which greatly increases the case fatality rate. Moreover, there is no effective drug that can resist the novel coronavirus so far, so it’s urgent to develop antiviral drug for the SARS-CoV-2. In our research, we screened 29 compounds with a score lower than -6 from 35 flavonoid compounds by molecular docking. (-)-Gallocatechin gallate, (+)-Gallocatechin and Baicalein were identified to have potent inhibit activity with IC50 5.774±0.805μM, 13.14±2.081μM and 5.158±0.928μM by FRET assay. Subsequently, we conducted molecular docking experiments, which showed that (-)-Gallocatechin gallate, (+)-Gallocatechin and Baicalein were non-covalently bound to Mpro through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of (-)-Gallocatechin gallate and Baicalein on cytokine storm use a mouse model of sepsis. (-)-Gallocatechin gallate and Baicalein significant reduced sepsis severity based on weight, murine sepsis score and survival rate and reduced the inflammatory factors level such as TNF-α, IL-1α, IL-4 and IL-10. Overall, (-)-Gallocatechin gallate and Baicalein may be potential drugs for symptomatic treatment of COVID-19.

scholarly journals The Interaction Between Pulmonary Fibrosis and COVID-19 and the Application of Related Anti-Fibrotic Drugs

2022 ◽  
Vol 12 ◽  
Author(s):  
Hao Shen ◽  
Nu Zhang ◽  
Yuqing Liu ◽  
Xuerong Yang ◽  
Yuanyuan He ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Drug Treatment ◽  
Immune Cells ◽  
Distress Syndrome ◽  
Potential Interaction ◽  
Inflammatory Factors ◽  
Treatment Programs ◽  
Cytokine Storm ◽  
Potential Mechanism ◽  
Drug Treatment Program

COVID-19 is a highly contagious respiratory disease, which mainly affects the lungs. Critically ill patients are easily complicated by cytokine storms, acute respiratory distress syndrome (ARDS), and respiratory failure, which seriously threaten their lives. Pulmonary fibrosis (PF) is a common interstitial lung disease, and its pathogenesis may involve the participation of a variety of immune cells and inflammatory factors. Current studies have shown that patients with COVID-19 may be complicated by pulmonary fibrosis, and patients with pulmonary fibrosis may also be at higher risk of contracting COVID-19 than healthy people. Pulmonary fibrosis is an important risk factor leading to the aggravation of COVID-19 disease. COVID-19 complicated by cytokine storm and ARDS mechanism pathways are similar to the pathogenesis of pulmonary fibrosis. The potential interaction between pulmonary fibrosis and COVID-19 can cause acute exacerbation of the patient’s condition, but the potential mechanism between the two has not been fully elucidated. Most of the drug treatment programs for COVID-19-related pulmonary fibrosis are currently formulated about the relevant guidelines for idiopathic pulmonary fibrosis (IPF), and there is no clear drug treatment program recommendation. This article aims to summarize the relevant mechanism pathways of COVID-19 and pulmonary fibrosis, explore the interrelationships and possible mechanisms, and discuss the value and risks of existing and potential COVID-19-related pulmonary fibrosis treatment drugs, to provide reference for anti-fibrosis treatment for patients.

scholarly journals Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1084
Author(s):  
Junya Ono ◽  
Masayuki Takai ◽  
Ayami Kamei ◽  
Yoshinori Azuma ◽  
Kenji Izuhara
Keyword(s):  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Biological Fluids ◽  
Allergic Inflammation ◽  
Transforming Growth Factor Β ◽  
Serum Levels ◽  
Vital Role ◽  
Interleukin 4 ◽  
Type 2 Inflammation

Periostin is known to be a useful biomarker for various diseases. In this article, we focus on allergic diseases and pulmonary fibrosis, for which we and others are now developing detection systems for periostin as a biomarker. Biomarker-based precision medicine in the management of type 2 inflammation and fibrotic diseases since heterogeneity is of utmost importance. Periostin expression is induced by type 2 cytokines (interleukin-4/-13) or transforming growth factor-β, and plays a vital role in the pathogenesis of allergic inflammation or interstitial lung disease, respectively, andits serum levels are correlated disease severity, prognosis and responsiveness to the treatment. We first summarise the importance of type 2 biomarker and then describe the pathological role of periostin in the development and progression of type 2 allergic inflammation and pulmonary fibrosis. In addition, then, we summarise the recent development of assay methods for periostin detection, and analyse the diseases in which periostin concentration is elevated in serum and local biological fluids and its usefulness as a biomarker. Furthermore, we describe recent findings of periostin as a biomarker in the use of biologics or anti-fibrotic therapy. Finally, we describe the factors that influence the change in periostin concentration under the healthy conditions.

scholarly journals Lipopolysaccharides promote pulmonary fibrosis in silicosis through the aggravation of apoptosis and inflammation in alveolar macrophages

2020 ◽  
Vol 15 (1) ◽  
pp. 598-605
Author(s):  
Shiyi Tan ◽  
Shang Yang ◽  
Mingke Chen ◽  
Yurun Wang ◽  
Li Zhu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Alveolar Macrophages ◽  
Inflammatory Factors ◽  
Necrosis Factor Alpha ◽  
Defensive Role ◽  
Factor Alpha ◽  
Apoptosis And Inflammation ◽  
The Relationship ◽  
Lps Treatment ◽  
Necrosis Factor

AbstractAlveolar macrophages (AMs) play an important defensive role by removing dust and bacteria from alveoli. Apoptosis of AMs is associated with lung fibrosis; however, the relationship between this apoptotic event and environmental factors, such as the presence of lipopolysaccharides (LPSs) in the workplace, has not yet been addressed. To investigate whether exposure to LPS can exacerbate fibrosis, we collected AMs from 12 male workers exposed to silica and incubated them in the presence and absence of LPS for 24 h. We show that the levels of cleaved caspase-3 and pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha were increased in these AMs following LPS treatment. Moreover, we demonstrate that LPS exposure aggravated apoptosis and the release of inflammatory factors in AMs in a mouse model of silicosis, which eventually promoted pulmonary fibrosis. These results suggest that exposure to LPS may accelerate the progression of pulmonary fibrosis in silicosis by increasing apoptosis and inflammation in AMs.

C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cells

2021 ◽  
Author(s):  
Sisi Yan ◽  
Jinli Ding ◽  
Yi Zhang ◽  
Jiayu Wang ◽  
Sainan Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Models ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Reactive Protein ◽  
Reproductive Endocrine ◽  
Factor Α

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.

scholarly journals FRI0416 COMBINATION OF SERUM ADIPOKINES/RELATED INFLAMMATORY FACTORS AND RATIOS AS PREDICTORS OF INFRAPATELLAR FAT PAD VOLUME IN KNEE OSTEOARTHRITIS PATIENTS: USAGE OF A COMPREHENSIVE MACHINE LEARNING APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 806.1-807
Author(s):  
H. Bonakdari ◽  
G. Tardif ◽  
F. Abram ◽  
J. P. Pelletier ◽  
J. Martel-Pelletier
Keyword(s):  
Risk Factors ◽  
Serum Levels ◽  
Infrapatellar Fat Pad ◽  
Inflammatory Factors ◽  
Fat Pad ◽  
Research Support ◽  
Knee Oa ◽  
Total Cohort ◽  
Low Bmi ◽  
The University

Background:One of the hurdles in osteoarthritis (OA) drug discovery and the improvement of therapeutic approaches is the early identification of patients who will progress. It is therefore crucial to find efficient and reliable means of screening OA progressors. Although the main risk factors, age, gender and body mass index (BMI), are important, they alone are poor predictors. However, serum factors could be potential biomarkers for early prediction of knee OA progression.Objectives:In a first step toward finding early reliable predictors of OA progressors, this study aimed to determine, in OA individuals, the optimum combination of serum levels of adipokines/related inflammatory factors, their ratios, and the three main OA risk factors for predicting knee OA infrapatellar fat pad (IPFP) volume, as this tissue has been associated with knee OA onset and progression.Methods:Serum and magnetic resonance images (MRI) were from the Osteoarthritis Initiative at baseline. Variables (48) comprised the 3 main OA risk factors (age, gender, BMI), 6 adipokines, 3 inflammatory factors, and their 36 ratios. IPFP volume was assessed on MRI with a neural network methodology. The best variables and models were identified in Total cohort (n=678), High-BMI (n=341) and Low-BMI (n=337), using an artificial intelligence selection approach: the adaptive neuro-fuzzy inference system embedded with fuzzy c-means clustering (ANFIS-FCM). Performance was validated using uncertainty analyses and statistical indices. Reproducibility was done using 80 OA patients from a clinical trial (female, n=57; male, n=23).Results:For the three groups, 8.44E+14 sub-variables were investigated and 48 models were selected. The best model for each group included five variables: the three risk factors and adipsin/C-reactive protein combined for Total cohort, adipsin/chemerin; High-BMI, chemerin/adiponectin high molecular weight; and Low-BMI, interleukin-8. Data also revealed that the main form of the ratio used for the model was justified, as the use of the inverse form slightly decreased the performance of the model in both training and testing stages. Further investigation indicated that gender improved (13-16%) the prediction results compared to the BMI-based models. For each gender, we then generated a pseudocode (an evolutionary computation equation) with the 5 variables for predicting IPFP volume. Reproducibility experiments were excellent (correlation coefficient: female 0.83, male 0.95).Conclusion:This study demonstrates, for the first time, that the combination of the serum levels of adipokines/inflammatory factors and the three main risk factors of OA could predict IPFP volume with high reproducibility, and superior performance with gender separation. By using the models for each gender and the pseudocodes for OA patients provided in this study, the next step will be to develop a predictive model for OA progressors.Acknowledgments:This work was funded by the Chair in Osteoarthritis of the University of Montreal, the Osteoarthritis Research Unit of the University of Montreal Hospital Research Centre, the Groupe de recherches des maladies rhumatismales du Québec and by ArthroLab Inc., all from Montreal, Quebec, Canada.Disclosure of Interests:Hossein Bonakdari: None declared, Ginette Tardif: None declared, François Abram Employee of: ArthroLab Inc., Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Johanne Martel-Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica

MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium

2016 ◽  
Vol 44 (06) ◽  
pp. 1111-1125 ◽  
Author(s):  
Muhammad Jahangir Hossen ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho
Keyword(s):  
Mouse Model ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Elevated Serum ◽  
Human Monocyte ◽  
Serum Levels ◽  
Mitogen Activated Protein Kinase ◽  
Xanthium Strumarium ◽  
U937 Cells ◽  
Anti Inflammatory

Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a combination therapy of bosentan and imatinib

2015 ◽  
Vol 41 (4) ◽  
pp. 173-188 ◽  
Author(s):  
Shanmuga Reddy Chilakapati ◽  
Mamatha Serasanambati ◽  
Prabhakar Vissavajjhala ◽  
Jagadeeshwara Reddy Kanala ◽  
Damodar Reddy Chilakapati
Keyword(s):  
Pulmonary Fibrosis ◽  
Combination Therapy ◽  
Mouse Model

scholarly journals Probable Neuropsychological & Cognitive Complications due to Cytokine Storm in Patients With COVID-19

2021 ◽  
Vol 0 (0) ◽  
pp. 1-37
Author(s):  
Zahra Keshtgar ◽  
◽  
GH. Reza Chalabianloo ◽  
Niloofar Esmaeili ◽  
◽  
...  
Keyword(s):  
Nervous System ◽  
Case Reports ◽  
Case Series ◽  
Executive Dysfunction ◽  
Inflammatory Factors ◽  
Cytokine Storm ◽  
Case Control Studies ◽  
Necrosis Factor Alpha ◽  
Cross Sectional ◽  
Tnf Α

Introduction: COVID-19 (coronavirus disease 2019) was identified in China in December 2019 for the first time and is rapidly spreading throughout the world as a pandemic. As COVID-19 causes mild to severe acute respiratory syndrome, most studies in this context have focused on pathogenesis primarily in the respiratory system. However, evidence shows that the central nervous system (CNS) may also be affected by COVID-19. Since COVID-19 is spreading, it is imperative to study its possible cognitive effects in patients suffering and recovering from COVID-19. Methods: The articles used in this study were searched by keywords such as Cytokine storm and covid-19, covid-19 and executive dysfunction, cognitive disorder and covid-19, CNS and covid 19, Coronavirus, Neuroinvasion in science direct, Scopus, PubMed, Embase, and Web of Science databases based on Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. The study will assess all observational studies published between December 2019 and April 2021 in peer-reviewed journals, including cross-sectional, cohort, case-control studies, case reports and case series. The search result was 106 articles, of which 73 articles related to Covid-19, the stages of infection by this virus, its effect on the nervous system and neurological symptoms, the cytokine storm caused by this infection, and the possible cognitive consequences caused by this virus in patients, has been reviewed. Other articles were not checked due to their limited relevance to the topic under discussion. Results: Studies show that neurons may be directly affected by SARS-CoV-1 and SARS-CoV-2. Furthermore, various studies indicate that systemic inflammation (so-called "cytokine storm") is also responsible for brain damage induced by infection with SARS-CoV-1 and SARS-CoV-2. Such a way that this patients showed elevated levels of interleukin (IL-), 6, 8, and 10 and of tumor necrosis factor-alpha (TNF- α) in their blood. Conclusion: Various cognitive defects following an increase level of cytokines such as TNF-α and IL-6,8 have been observed. Therefore, due to the increase level of these pro-inflammatory factors in the brains of these patients, cognitive deficits can be expected, which need further investigation.

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