Article of the Year 2021
COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing HyperinflammationRead the full article
Mediators of Inflammation publishes papers on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules
Chief Editor, Professor Agrawal, is an Assistant Clinical Professor of the Division of Basic and Clinical Immunology. Dr. Agrawal's research focuses on the dendritic cells of the immune system in the context of aging and autoimmunity.
Latest ArticlesMore articles
Role of Ezrin in Asthma-Related Airway Inflammation and Remodeling
Ezrin is an actin binding protein connecting the cell membrane and the cytoskeleton, which is crucial to maintaining cell morphology, intercellular adhesion, and cytoskeleton remodeling. Asthma involves dysfunction of inflammatory cells, cytokines, and airway structural cells. Recent studies have shown that ezrin, whose function is affected by extensive phosphorylation and protein interactions, is closely associated with asthma, may be a therapeutic target for asthma treatment. In this review, we summarize studies on ezrin and discuss its role in asthma-related airway inflammation and remodeling.
Amentoflavone Exerts Anti-Neuroinflammatory Effects by Inhibiting TLR4/MyD88/NF-κB and Activating Nrf2/HO-1 Pathway in Lipopolysaccharide-Induced BV2 Microglia
Background. Amentoflavone, a natural biflavone, exerts anti-inflammation, antioxidation, and antiapoptosis effects on many diseases. However, the mechanism of amentoflavone on neuroinflammation-related diseases has not been comprehensively examined clearly. Methods. BV2 microglial cells were treated with amentoflavone (10 μM), followed by lipopolysaccharide (LPS). Microglial activation and migration ability and the expression of proinflammatory cytokines and other signaling proteins were determined using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and wound-healing assays. Results. Amentoflavone restored LPS-induced microglia activation, migration, and inflammation response which depends on regulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway. In addition, amentoflavone also enhanced nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) levels in LPS-treated BV2 microglial cells. Conclusions. Amentoflavone ameliorated LPS-induced neuroinflammatory response and oxidative stress in BV2 microglia. These data provide new insight into the mechanism of amentoflavone in the treatment of neuroinflammation-related diseases. Therefore, amentoflavone may be a potential therapeutic option for neurological disorders.
Elevated Serum Levels of CCL23 Are Associated with Poor Outcome after Resection of Biliary Tract Cancer
Background. Surgical tumor resection is the only potentially curative treatment option for patients with biliary tract cancer (BTC). However, 5-year survival rates are still below 50% mainly due to tumor recurrence. The preoperative identification of ideal surgical candidates has remained a major challenge and easily accessible algorithms including parameters of the individual tumor biology are missing. Chemokine (C-C motif) ligand 23 (CCl23) has been associated with tumor progression in hepatocellular carcinoma (HCC), but its role in the context of BTC is largely unknown. Here, we evaluated circulating levels of CCL23 as potential diagnostic and prognostic biomarker in patients with resectable BTC. Methods. CCl23 serum levels were analyzed by multiplex immunoassay in a cohort of 119 BTC patients receiving surgical tumor resection as well as 50 healthy control samples and 11 patients with primary sclerosing cholangitis (PSC). Results. Baseline serum CCL23 levels were significantly elevated in BTC patients compared to PSC patients as well as healthy controls. CCL23 increased the diagnostic sensitivity and specificity of established tumor markers including CA19-9 and correlated with patients’ age and makers of systemic inflammation. Elevated preoperative CCL23 levels were associated with a significantly impaired postoperative outcome. BTC patients with a preoperative CCL23 level above the optimal prognostic cut-off value of 702.4 pg/ml showed a median OS of only 110 days compared to 501 days for patients with low initial CCL23 levels. The prognostic value of circulating CCL23 was confirmed in Cox-regression analysis. Conclusion. Serum levels of CCL23 are elevated in patients with BTC, and high preoperative CCL23 levels were associated with an impaired postoperative survival. CCL23 serum levels could help to identify the ideal surgical candidates for BTC resection in the future.
The Effect of Pomegranate Juice and Sumac Consumption in the Treatment of Outpatients with COVID-19
Introduction. COVID-19, an epidemic of coronavirus infection, has become a major global threat. The coronavirus mainly targets the human respiratory system, followed by cytokine storm, and altered immune responses associated with disease progression and adverse outcomes. Sumac and pomegranate juice are rich in bioactive compounds, which potentially have antiviral activities. This study is aimed at investigating the effect of a diet based on the use of sumac and pomegranate juice on the treatment of outpatients with COVID-19. Methods. In this study, 182 outpatients with COVID-19 were randomly divided into two groups receiving a diet containing pomegranate juice and sumac along with standard treatment and the control group (group 2) receiving standard treatment. Results. Consumption of a diet containing pomegranate juice and sumac in outpatients with COVID-19, who were receiving standard-of-care treatment, led to a significant decrease in fever, chills, cough, weakness, smell and taste disorders, shortness of breath, diarrhea, nausea and vomiting, and abdominal pain compared with outpatients with COVID-19 who received only standard treatment. Conclusion. Clinical trials of outpatients have limitations such as patients’ resilience to post-COVID-19 follow-up. However, the use of pomegranate juice and sumac can be efficacious in reducing COVID-19 symptoms. This trial is registered with IRCT20190406043175N3.
Vitamin D3 Supplementation Attenuates Surgery-Induced Neuroinflammation and Cognitive Impairment by Regulating NLRP3 Inflammasome in Mice
Neuroinflammation plays a dominant role in the progression of postoperative cognitive dysfunction (POCD). Vitamin D has been known to have important regulatory functions in inflammation and immune response. The NOD-like receptor protein 3 (NLRP3) is an essential inflammasome in the inflammatory response and could be activated by anesthesia and surgery. In this study, male C57BL/6 mice aged 14–16 months were given VD3 for 14 days straight before having an open tibial fracture surgery. The animals were either sacrificed to obtain the hippocampus or tested in a Morris water maze test. Western blot was employed to estimate the levels of NLRP3, ASC, and caspase-1, immunohistochemistry was used to identify microglial activation, and an enzyme-linked immunosorbent assay was used to measure the expression of IL-18 and IL-1β, while using the corresponding assay kits to assess ROS and MDA levels to reflect the oxidative stress status. We showed that VD3 pretreatment significantly improved surgery-induced memory and cognitive dysfunctions in aged mice, which was linked to the inactivation of the NLRP3 inflammasome and the inhibition of neuroinflammation. This finding provided a novel preventative strategy for clinically reducing postoperative cognitive impairment in elderly surgical patients. This study has some limitations. Gender differences in the effects of VD3 were not considered, and only male mice were used. Additionally, VD3 was given as a preventative measure; however, it is unknown whether it has any therapeutic benefits for POCD mice. This trial is registered with ChiCTR-ROC-17010610.
Significance of Exhaled Nitric Oxide and Carbon Monoxide in Auxiliary Diagnosis and Evaluation of Allergic Rhinitis
Objective. The concentration of exhaled NO and CO is considered as a candidate marker of respiratory inflammatory disease. This report discusses the exhaled NO and CO in the auxiliary diagnosis and evaluation of allergic rhinitis (AR). Methods. 60 AR patients from October 2017 to March 2019, compared with 30 healthy controls. The severity of AR disease was distinguished by symptom score. Both groups were tested for exhaled nitric oxide through the nose or mouth and exhale carbon monoxide through the mouth. AR patients received glucocorticoid nasal spray for 1 month and were tested again for nNO, eNO, eCO, and symptom score. Results. Before treatment, all the nNO, eNO, and eCO of the AR group were higher than the control group. There were differences in the severe and moderate subgroup: . eCO was not significantly different between the mild and control groups. The nNO, eNO, and eCO levels were positively correlated with symptom score. After treatment, nNO decreased significantly in the three subgroups; eNO and eCO in the severe AR group decreased significantly. Drawing the ROC curve, the area under curve (AUC) of nNO is 0.978. The AUC of eNO and eCO was 0.786 and 0.577, respectively. Conclusion. The nNO, eNO, and eCO in the AR group are higher than healthy people, which positively correlated with the severity of AR symptoms. The detection of nNO, eNO, and eCO can monitor the changes of AR. The detection of nNO level as an indicator of AR auxiliary diagnosis has high accuracy.