Upregulation of Biomarker Limd1 Was Correlated with Immune Infiltration in Doxorubicin-Related CardiotoxicityRead 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.
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Fibrinogen Is Associated with Prognosis of Critically Ill Patients with Sepsis: A Study Based on Cox Regression and Propensity Score Matching
Introduction. Sepsis is a common syndrome in critically ill patients. Fibrinogen was reported to be associated with the prognosis of sepsis patients. Materials and Methods. Data was acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression was utilized to estimate the relationship between fibrinogen and inhospital mortality. The cumulative incidence of mortality by fibrinogen level was estimated through the Kaplan-Meier curve. Restricted cubic spline (RCS) was used to assess nonlinear relationship. Subgroup analysis was also conducted to evaluate the robustness of the association between fibrinogen and inhospital mortality. Propensity score matching (PSM) was applied to adjust for confounding factors. Results. A total of 3365 patients, including 2031 survivors and 1334 nonsurvivors, were enrolled in our study. The survivors had a significantly elevated levels of fibrinogen compared with the deceased. The elevated level of fibrinogen was significantly associated with a decrease in mortality in multivariate Cox regression before and after PSM (HR 0.66, and HR 0.73, , respectively). RCS showed a nearly linear relationship. Subgroup analysis demonstrated the robustness of the association in most subpopulations. However, the association between decreased levels of fibrinogen and increased inhospital mortality was denied after PSM. Conclusion. The elevated level of fibrinogen hints at better overall survival in critically ill patients with sepsis. Decreased levels of fibrinogen may be of little value in identifying patients with a high risk of death.
Mechanism of SET8 Activates the Nrf2-KEAP1-ARE Signaling Pathway to Promote the Recovery of Motor Function after Spinal Cord Injury
Background. Spinal cord injury (SCI) is a common injury of the central nervous system (CNS), and astrocytes are relatively abundant glial cells in the CNS that impairs the recovery of motor function after SCI. It was confirmed that the oxidative stress of mitochondria leads to the accumulation of reactive oxygen species (ROS) in cells, which plays a key role in the motor function of astrocytes. However, the mechanism by which oxidative stress affects astrocyte motility after SCI is still unexplained. Therefore, this study investigated the influence of SET8-regulated oxidative stress on astrocyte autophagy levels after SCI in rats and the potential mechanisms of action. Methods. We used real-time quantitative PCR, western blotting, and immunohistochemical staining to analyze SET8, Keap1, and Nrf2 expression at the cellular level and in SCI tissues. ChIP to detect H4K20me1 enrichment in the Keap1 promoter region under OE-SET8 (overexpression of SET8) conditions. Western blotting was used to assess the expression of signature proteins of astrocytes, proteins associated with autophagy, proteins associated with glial scar formation, reactive oxygen species (ROS) levels in cells using DHE staining, and astrocyte number, morphological alterations, and induction of glial scar formation processes using immunofluorescence. In addition, the survival rate of neurons after SCI in rats was examined by using NiSSl staining. Results. OE-SET8 upregulates the enrichment of H4K20me1 in Keap1, inhibits Keap1 expression, activates the Nrf2-ARE signaling pathway to suppress ROS accumulation, inhibits oxidative stress-induced autophagy and glial scar formation in astrocytes, and leads to reduced neuronal loss, which promoted the recovery and improvement of motor function after SCI in rats. Conclusion. Overexpression of SET8 alleviated oxidative stress by regulating Keap1/Nrf2/ARE, inhibited astrocyte autophagy levels, and reduced glial scar formation as well as neuronal loss, thereby promoting improved recovery of motor function after SCI. Thus, the SET8/H4K20me1 regulatory function may be a promising cellular therapeutic intervention point after SCI.
TIRAP, TRAM, and Toll-Like Receptors: The Untold Story
Toll-like receptors (TLRs) are the most studied receptors among the pattern recognition receptors (PRRs). They act as microbial sensors, playing major roles in the regulation of the innate immune system. TLRs mediate their cellular functions through the activation of MyD88-dependent or MyD88-independent signaling pathways. Myd88, or myeloid differentiation primary response 88, is a cytosolic adaptor protein essential for the induction of proinflammatory cytokines by all TLRs except TLR3. While the crucial role of Myd88 is well described, the contribution of other adaptors in mediating TLR signaling and function has been underestimated. In this review, we highlight important results demonstrating that TIRAP and TRAM adaptors are also required for full signaling activity and responses induced by most TLRs.
IFN-α-2b Reduces Postoperative Arthrofibrosis in Rats by Inhibiting Fibroblast Proliferation and Migration through STAT1/p21 Signaling Pathway
Objective. To investigate the effect of IFN-α-2b in preventing postoperative arthrofibrosis in rats, its antiproliferation effect on fibroblasts in vitro, and its molecular mechanism. Methods. The rat model of arthrofibrosis was established and treated with different concentrations of drugs. Knee specimens were collected for histological and immunohistochemical staining to observe the effect of IFN-α-2b on arthrofibrosis in rats. The biological information was further mined according to the database data, and the possible regulatory mechanism of IFN-α-2b on fibroblasts was analyzed. The inhibitory effect of IFN-α-2b on fibroblast proliferation and migration in vitro was detected by cell counting kit-8 (CCK-8), immunofluorescence analysis, cell cycle test, EdU assay, wound healing test, and Transwell method, and the analysis results were verified by Western blotting method. Results. The test results of rat knee joint specimens showed that IFN-α-2b significantly inhibited the degree of fibrosis after knee joint surgery, the number of fibroblasts in the operation area was less than that of the control group, and the expression of collagen and proliferation-related proteins decreased. In vitro experimental results show that IFN-α-2b can inhibit the proliferation and migration of fibroblasts. According to the results of database analysis, it is suggested that the STAT1/P21 pathway may be involved, and it has been verified and confirmed by Western blotting and other related methods. Conclusion. IFN-α-2b can reduce surgery-induced arthrofibrosis by inhibiting fibroblast proliferation and migration, which may be related to the regulation of STAT1/p21 signaling pathway.
Heparin-Binding Protein in Bronchoalveolar Lavage Fluid as a Biomarker for Discriminating Severe Bacterial and Viral Pneumonia in Critically Ill Children
Objective. This study is aimed at exploring the ability to use heparin-binding protein (HBP) in bronchoalveolar lavage fluid (BALF) to differentially diagnose bacterial infection from viral infection for severe community-acquired pneumonia (CAP) in critically ill children. Methods. A total of 181 children with severe CAP admitted to the intensive care unit (ICU) were included in this study. BALF and blood samples were collected within the first 24 hours of admission. BALF HBP and interleukin-6 (IL-6) concentrations and neutrophil percentage (N%) as well as blood HBP, IL-6, procalcitonin (PCT), C-reactive protein, white blood cell concentrations and N% were measured. Results. Of the enrolled children, 126 were confirmed to have bacterial pneumonia, and 55 were confirmed to have viral pneumonia. Blood HBP and PCT concentrations and N% and BALF HBP and IL-6 concentrations and N% were significantly higher in bacterial pneumonia than in viral pneumonia (). In the bacterial pneumonia group, HBP and IL-6 concentrations and N% in BALF samples were all significantly higher than those in blood samples (), and BALF HBP and IL-6 concentrations and N% were correlated with blood HBP and IL-6 concentrations and N%, respectively (, 0.250, and 0.235, ). BALF N% and blood N% were both correlated with BALF HBP concentrations and blood HBP concentrations, respectively ( and 0.346, ). ROC analysis revealed that BALF HBP showed the best ability to predict bacterial pneumonia, with an area under the curve of 0.994, a sensitivity of 95.24%, and a specificity of 100.00% at its optimal cutoff value of 74.05 ng/mL. Conclusion. BALF HBP might be a promising biomarker for the early discrimination of bacterial infection from viral infection in critically ill children with severe CAP.
Consensus Clustering and Survival-Related Genes of Cuproptosis in Cutaneous Melanoma
As a highly malignant tumor, the morbidity and mortality of cutaneous melanoma (CM) are increasing year by year. A novel type of cell death connected to mitochondrial metabolism is called cuproptosis. Cuproptosis regulates tumor biological behavior. Thus, genes controlling cuproptosis could be a promising candidate bioindicator for cancer therapy. Datasets of CM patients were obtained from the public database that includes clinical information and RNA-seq data. We divided CM patients into three different subgroups by unsupervised clustering method and explored the differences in functional pathways among the three subgroups by GSVA to prove the possible potential mechanism of copper death-related genes in the formation and development of CM. Secondly, we used differential analysis and Cox regression analysis to find the differential genes related to prognosis, constructed the CRG score, found the critical score for dividing high and low CRG score groups, and then analyzed the prognosis and immune infiltration of high and low CRG score groups. The results show a great correlation between OS and CRG scores. Compared with patients with high CRG scores, patients with low CRG scores have a significantly higher survival rate. In a word, copper sagging plays a certain role in the progress of CM.