Circulating IGFBP-3 and Interleukin 6 as Predictors of Osteoporosis in Postmenopausal Women: A Cross-Sectional StudyRead 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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Identification of GPD1L as a Potential Prognosis Biomarker and Associated with Immune Infiltrates in Lung Adenocarcinoma
Lung adenocarcinoma (LUAD) is one of the most prevalent pathological kinds of lung cancer, which is a common form of cancer that has a high death rate. Over the past several years, growing studies have indicated that GPD1L was involved in the advancement of a number of different cancers. However, its clinical significance in LUAD has not been investigated. In this study, following an examination of the TGCA datasets, we found that GPD1L displayed a dysregulated state in a wide variety of cancers; this led us to believe that GPD1L is an essential regulator in the progression of malignancies. In addition, we found that the expression of GPD1L was much lower in LUAD tissues when compared with nontumor specimens. According to the findings of ROC tests, GPD1L was able to effectively identify LUAD specimens from nontumor samples with an AUC value of 0.828 (95% confidence interval: 0.793 to 0.863). On the basis of the clinical study, a low expression of GPD1L was clearly related with both the N stage and the clinical stage. Moreover, based on the findings of a Kaplan-Meier survival study, elevated GPD1L expression was a strong indicator of considerably improved overall survival (OS) and disease-specific survival (DSS). GPD1L expression and clinical stages were found to be independent prognostic indicators for overall survival and disease-free survival in LUAD patients, according to multivariate analyses. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram demonstrated an effective prediction performance for LUAD patients. Besides, the expression of GPD1L was positively related to mast cells, eosinophils, Tcm, TFH, iDC, DC, and macrophages, while negatively associated with Th2 cells, NK CD56dim cells, Tgd, Treg, and neutrophils. Finally, qRT-PCR was able to demonstrate that GPD1L had a significant amount of expression in LUAD. Additionally, according to the results of functional tests, overexpression of GPD1L had a significant inhibiting effect on the proliferation of LUAD cells. In general, the results of our study suggested that GPD1L had the potential to serve as a diagnostic and prognostic marker for LUAD.
T Cell Subsets and the Expression of Related MicroRNAs in Patients with Recurrent Early Pregnancy Loss
This study explored the role of T cell subsets and the expression of related microRNAs in patients with recurrent early pregnancy loss (EPL). Fifty patients with EPL loss between May 2018 and May 2021 were randomly selected as the EPL group, and 50 pregnant women with normal pregnancies or normal delivery outcomes were randomly selected as the control group. The expression levels of T cell subset-related markers and T cell subset-related miRNAs, in addition to the frequencies of T cell subsets, in peripheral blood of the two groups were analyzed. In terms of T cell-related markers, the results showed that the expression levels of the transcriptional regulator TBX-21 (T-bet) and interferon regulatory factor 4 (IRF4) were significantly upregulated in peripheral blood of the patients in the EPL group (), whereas the expression levels of GATA binding protein 3 (GATA3) and glucocorticoid-induced tumor necrosis factor receptor (GITR) were significantly downregulated (). In the EPL group, the expression of mir-106b, mir-93, and mir-25 was upregulated (, , and , respectively) in regulatory T (Treg) cell-related T cell subsets, whereas the expression of miR-146a and miR-155 was downregulated (). The frequencies of Treg and exhausted T cells in the EPL group were significantly lower than those in the control group (). The cell frequencies of T helper 17 (Th17) cells and exhausted Treg cells in the EPL group were significantly higher than those in the control group (). In conclusion, immune cells and associated miRNA profiles can be used as prognostic biomarkers for the treatment of human reproductive disorders, such as EPL.
COX7B Is a New Prognostic Biomarker and Correlates with Tumor Immunity in Esophageal Carcinoma
Esophageal carcinoma (ESCA) refers to the most common type of malignant tumor, which reveals that it occurs often all over the world. ESCA is also correlated with an advanced stage and low survival rates. Thus, the development of new prognostic biomarkers is an absolute necessity. In this study, the aim was to investigate the potential of COX7B as a brand-new predictive biomarker for ESCA patients. COX7B expression in pancancer was examined using TIMER2. The statistical significance of the predictive value of COX7B expression was explored. The relationship between COX7B expression and tumor-infiltrating immune cells in ESCA was analyzed by using ssGSEA. In this study, the result indicated that several types of cancers had an abnormally high amount of COX7B. COX7B expression in samples from patients with ESCA was considerably higher than in nontumor tissues. A more advanced clinical stage may be anticipated from higher COX7B expression. According to the findings of Kaplan-Meier survival curves, patients with low COX7B levels had a more favorable prognosis than those with high COX7B levels. The result of multivariate analysis suggested that COX7B expression was a standalone prognostic factor for the overall survival of ESCA patients. A prognostic nomogram including gender, clinical stage, and COX7B expression was constructed, and TCGA-based calibration plots indicated its excellent predictive performance. An analysis of immune infiltration revealed that COX7B expression has a negative correlation with TFH, Tcm, NK cells, and mast cells. COX7B may serve as an immunotherapy target and as a biomarker for ESCA diagnosis and prognosis.
Upregulation of Biomarker Limd1 Was Correlated with Immune Infiltration in Doxorubicin-Related Cardiotoxicity
Doxorubicin is one of the most common antitumor drugs. However, cardiotoxicity’s side effect limits its clinical applicability. In the present study, Gene Expression Omnibus (GEO) datasets were applied to reanalyze differentially expressed genes (DEGs) and construct weighted correlation network analysis (WGCNA) modules of doxorubicin-induced cardiotoxicity in wild-type mice. Several other bioinformatics analyses were performed to pick out the hub gene, and then the correlation between the hub gene and immune infiltration was evaluated. In total, 120 DEGs were discovered in a mouse model of doxorubicin-induced cardiotoxicity, and PF-04217903, propranolol, azithromycin, etc. were found to be potential drugs against this pathological condition. Among all the DEGs, 14 were further screened out by WGCNA modules, of which Limd1 was upregulated and finally regarded as the hub gene after being validated in other GEO datasets. Limd1 was upregulated in the peripheral blood mononuclear cell (PBMC) of the rat model, and the area under curve (AUC) of the receiver operating characteristic curve (ROC) in diagnosing cardiotoxicity was 0.847. The GSEA and PPI networks revealed a potential immunocyte regulatory role of Limd1 in cardiotoxicity. The proportion of “dendritic cells activated” in the heart was significantly elevated, while “macrophage M1” and “monocytes” declined after in vivo doxorubicin application. Finally, Limd1 expression was significantly positively correlated with “dendritic cells activation’ and negatively correlated with “monocytes” and “macrophages M1’. In summary, our results suggested that limd1 is a valuable biomarker and a potential inflammation regulator in doxorubicin-induced cardiotoxicity.
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.