Mediators of Inflammation
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Acceptance rate20%
Submission to final decision93 days
Acceptance to publication24 days
CiteScore7.000
Journal Citation Indicator0.540
Impact Factor4.529

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 Hyperinflammation

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 Journal profile

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

 Editor spotlight

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.

 Special Issues

We currently have a number of Special Issues open for submission. Special Issues highlight emerging areas of research within a field, or provide a venue for a deeper investigation into an existing research area.

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Research Article

Identification of Diagnostic Genes and Effective Drugs Associated with Osteoporosis Treatment by Single-Cell RNA-Seq Analysis and Network Pharmacology

Background. Osteoporosis is a common bone metabolic disease with increased bone fragility and fracture rate. Effective diagnosis and treatment of osteoporosis still need to be explored due to the increasing incidence of disease. Methods. Single-cell RNA-seq was acquired from GSE147287 dataset. Osteoporosis-related genes were obtained from chEMBL. Cell subpopulations were identified and characterized by scRNA-seq, t-SNE, clusterProfiler, and other computational methods. “limma” R packages were used to identify all differentially expressed genes. A diagnosis model was build using rms R packages. Key drugs were determined by proteins-proteins interaction and molecular docking. Results. Firstly, 15,577 cells were obtained, and 12 cell subpopulations were identified by clustering, among which 6 cell subpopulations belong to CD45+ BM-MSCs and the other subpopulations were CD45-BM-MSCs. CD45- BM-MSCs_6 and CD45+ BM-MSCs_5 were consider as key subpopulations. Furthermore, we found 7 genes were correlated with above two subpopulations, and F9 gene had highest AUC. Finally, five compounds were identified, among which DB03742 bound well to F9 protein. Conclusions. This work discovered that 7 genes were correlated with CD45-BM-MSCs_6 and CD45+ BM-MSCs_5 subpopulations in osteoporosis, among which F9 gene had better research value. Moreover, compound DB03742 was a potential inhibitor of F9 protein.

Research Article

Exploration of Biomarkers of Psoriasis through Combined Multiomics Analysis

Background. Aberrant DNA methylation patterns are of increasing interest in the study of psoriasis mechanisms. This study aims to screen potential diagnostic indicators affected by DNA methylation for psoriasis based on bioinformatics using multiple machine learning algorithms and to preliminarily explore its molecular mechanisms. Methods. GSE13355, GSE14905, and GSE73894 were collected from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated region- (DMR-) genes between psoriasis and control samples were combined to obtain differentially expressed methylated genes. Subsequently, a protein-protein interaction (PPI) network was established to analyze the interaction between differentially expressed methylated genes. Moreover, the hub genes of psoriasis were screened by the least absolute shrinkage and selection operator (LASSO), Random Forest (RF), and Support Vector Machine (SVM), which were further performed single-gene gene set enrichment analysis (GSEA) to clarify the pathogenesis of psoriasis. The druggable genes were predicted using DGIdb. Finally, the expressions of hub genes in psoriasis lesions and healthy controls were detected by immunohistochemistry (IHC) and quantitative real-time PCR (RT-qPCR). Results. In this study, a total of 767 DEGs and 896 DMR-genes were obtained. Functional enrichment showed that they were significantly associated with skin development, skin barrier function, immune/inflammatory response, and cell cycle. The combined transcriptomic and DNA methylation data resulted in 33 differentially expressed methylated genes, of which GJB2 was the final identified hub gene for psoriasis, with robust diagnostic power. IHC and RT-qPCR showed that GJB2 was significantly higher in psoriasis samples than those in healthy controls. Additionally, GJB2 may be involved in the development and progression of psoriasis by disrupting the body’s immune system, mediating the cell cycle, and destroying the skin barrier, in addition to possibly inducing diseases related to the skeletal aspects of psoriasis. Moreover, OCTANOL and CARBENOXOLONE were identified as promising compounds through the DGIdb database. Conclusion. The abnormal expression of GJB2 might play a critical role in psoriasis development and progression. The genes identified in our study might serve as a diagnostic indicator and therapeutic target in psoriasis.

Research Article

Connexin 37 Regulates the Kv1.3 Pathway and Promotes the Development of Atherosclerosis

Objective. To investigate the mechanism of Connexin 37 (Cx37) and Kv1.3 pathways in atherosclerosis (AS). Methods. ApoE-/- mice were given a high-fat diet to establish atherosclerosis (AS) model, and macrophages in mice were isolated and extracted to transfect Cx37 vectors with silencing or overexpressing, and Kv1.3 pathway blockers were used to inhibit the pathway activity. The indexes of body weight, blood glucose, and blood lipid of mice were collected. The protein and mRNA expression levels of Cx37 and Kv1.3 were detected by reverse transcription-PCR (RT-PCR), Western blot, and immunofluorescence technique. Oil red O staining was used to observe plaque area. Masson staining was used to detect collagen content. The concentrations of chemokine CCL7 were quantified using the ELISA kits. CCK8 was used to detect cell proliferation. Results. Cx37 and Kv1.3 were highly expressed in macrophages of AS mice, and the expression of Kv1.3 and CCL7 decreased after Cx37 was silenced, and the proliferation of macrophages was also decreased. Wild-type mice and AS model mice were treated with Cx37 overexpression vectors and Kv1.3 pathway blocking, and it was found that Cx37 overexpression could improve the blood lipid and blood glucose levels and increase the area of AS in AS mice. However, blocking the activity of Kv1.3 pathway can reduce the levels of blood lipid and blood glucose, increase the body weight of mice, and reduce the area of AS mice. Blocking the activity of Kv1.3 pathway can slow down the plaque development of AS mice and make its indexes close to wild-type mice. And the use of Kv1.3 pathway blockers on the basis of overexpression of Cx37 indicated that inhibition of Kv1.3 pathway activity did not affect the expression of Cx37, but could inhibit the collagen content in the plaque area of AS mice, inhibit the expression of chemokine CCL7, and reverse the effect of Cx37 overexpression. Conclusion. Cx37 can improve the activity of macrophages by regulating the expression of chemokines and the activity of Kv1.3 pathway in AS mice, and enrich macrophages in inflammatory tissues and expand the area of plaque formation.

Research Article

FAM171B as a Novel Biomarker Mediates Tissue Immune Microenvironment in Pulmonary Arterial Hypertension

The purpose of this study was to uncover potential diagnostic indicators of pulmonary arterial hypertension (PAH), evaluate the function of immune cells in the pathogenesis of the disease, and find innovative treatment targets and medicines with the potential to enhance prognosis. Gene Expression Omnibus was utilized to acquire the PAH datasets. We recognized differentially expressed genes (DEGs) and investigated their functions utilizing R software. Weighted gene coexpression network analysis, least absolute shrinkage and selection operators, and support vector machines were used to identify biomarkers. The extent of immune cell infiltration in the normal and PAH tissues was determined using CIBERSORT. Additionally, the association between diagnostic markers and immune cells was analyzed. In this study, 258DEGs were used to analyze the disease ontology. Most DEGs were linked with atherosclerosis, arteriosclerotic cardiovascular disease, and lung disease, including obstructive lung disease. Gene set enrichment analysis revealed that compared to normal samples, results from PAH patients were mostly associated with ECM-receptor interaction, arrhythmogenic right ventricular cardiomyopathy, the Wnt signaling pathway, and focal adhesion. FAM171B was identified as a biomarker for PAH (). The mechanism underlying PAH may be mediated by nave CD4 T cells, resting memory CD4 T cells, resting NK cells, monocytes, activated dendritic cells, resting mast cells, and neutrophils, according to an investigation of immune cell infiltration. FAM171B expression was also associated with resting mast cells, monocytes, and CD8 T cells. The results suggest that PAH may be closely related to FAM171B with high diagnostic performance and associated with immune cell infiltration, suggesting that FAM171B may promote the progression of PAH by stimulating immune infiltration and immune response. This study provides valuable insights into the pathogenesis and treatment of PAH.

Research Article

LncRNA MDRL Mitigates Atherosclerosis through miR-361/SQSTM1/NLRP3 Signaling

Objective. Long non-coding RNAs (lncRNAs) play many important roles in gene regulation and disease pathogenesis. Here, we sought to determine that mitochondrial dynamic related lncRNA (MDRL) modulates NLRP3 inflammasome activation and apoptosis of vascular smooth muscle cells (VSMCs) and protects arteries against atherosclerosis. Methods. In vivo experiments, we applied LDLR knockout (LDLR-/-) mice fed the high-fat diet to investigate the effects of MDRL on atherosclerosis. In vitro experiments, we applied mouse aortic smooth muscle cells to determine the mechanism of MDRL in abrogating NLRP3 inflammasome and inhibiting cell apoptosis through miR-361/sequentosome 1 (SQSTM1) by TUNEL staining, quantitative RT-PCR, western blot, microribonucleoprotein immunoprecipitation, and luciferase reporter assay. Results. Downregulated MDRL and increased NLRP3 were observed in mouse atherosclerotic plaques, accompanied with the increase of miR-361. The results showed that MDRL overexpression significantly attenuated the burden of atherosclerotic plaque and facilitated plaque stability through inhibiting NLRP3 inflammasome activation and cell apoptosis, and vice versa. Mechanically, MDRL suppressed NLRP3 inflammasome activation and VSMC apoptosis via suppressing miR-361. Furthermore, miR-361 directly bound to the 3’UTR of SQSTM1 and inhibited its translation, subsequently activating NLRP3 inflammasome. Systematic delivery of miR-361 partly counteracted the beneficial effects of MDRL overexpression on atherosclerotic development in LDLR-/- mice. Conclusions. In summary, MDRL alleviates NLRP3 inflammasome activation and apoptosis in VSMCs through miR-361/SQSTM1/NLRP3 pathway during atherogenesis. These data indicate that MDRL and inhibition of miR-361 represent potential therapeutic targets in atherosclerosis-related diseases.

Research Article

Inhibition of CEBPB Attenuates Lupus Nephritis via Regulating Pim-1 Signaling

Systemic lupus erythematosus (SLE) is an autoimmune disease leading to inflammatory damage in multiple target organs, and lupus nephritis (LN) is one of the most life-threatening organ manifestations. CCAAT/enhancer-binding protein β (CEBPB) regulates the NLRP3 inflammasome and is involved in the pathogenesis of SLE. However, the role and mechanism of CEBPB in LN remains unclear. MRL/lpr mice and lipopolysaccharides (LPS) combined with adenosine triphosphate- (ATP-) treated glomerular podocytes were used as models of LN in vivo and in vitro, respectively. In vivo, we investigated the expressions of CEBPB during the development of MRL/lpr mice. Then we assessed the effect of CEBPB inhibition on renal structure and function through injecting shCEBPB lentivirus into MRL/lpr mice. In vitro, glomerular podocytes were treated with Pim-1-OE and siCEBPB to explore the relation between CEBPB and Pim-1. The progression of LN in mice was associated with the increased level of CEBPB, and the inhibition of CEBPB ameliorated renal structure impairments and improved renal function damage associated with LN. Knockdown of CEBPB could suppress the activation of NLRP3 inflammasome and the secretion of IL-1β and IL-6. Furthermore, the knockdown of CEBPB could inhibit NLRP3 inflammasome activation and pyroptosis via binding to Pim-1 promoter to downregulate its expression, and the overexpression of Pim-1 reversed the effects of CEBPB deficiency. The regulation of CEBPB on Pim-1 facilitated pyroptosis by activating NLRP3 inflammasome, thereby promoting the development of LN.

Mediators of Inflammation
 Journal metrics
See full report
Acceptance rate20%
Submission to final decision93 days
Acceptance to publication24 days
CiteScore7.000
Journal Citation Indicator0.540
Impact Factor4.529
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Article of the Year Award: Outstanding research contributions of 2021, as selected by our Chief Editors. Read the winning articles.