An Aptamer-Based Antagonist against the Receptor for Advanced Glycation End-Products (RAGE) Blocks Development of Colorectal CancerRead 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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Assessment of the Vanillin Anti-Inflammatory and Regenerative Potentials in Inflamed Primary Human Gingival Fibroblast
Background. Inflammatory responses have been associated with delayed oral mucosal wound healing and the pathogenesis of the periodontal disease. The invasion of microbes into the tissues and the establishment of a chronic infection may be due to impaired healing. The protracted inflammatory phase may delay wound healing and probably support tissue fibrosis and reduce tissue regeneration. Vanillin is a well-known natural compound with potential anti-inflammatory capacity. Hence, we hypothesized that Vanillin could accelerate wound healing reducing inflammation and especially cytokine production making the oral tissue repair process easier. Methods. Our hypothesis was tested using primary human gingival fibroblast (HGF) cell pretreated with Vanillin and primed with IL-1β, as inductor of proinflammatory environment. After 24 hours of treatments, the gene expression and production of IL-6, TNF-α, IL-8, COX-2, iNOS, and nitric oxide (NO) generation and the wound healing rate were determined. Results. In IL-1β-primed cells, preincubation with Vanillin reduced IL-6, IL-8, COX-2, and iNOS expression and NO release, compared to IL-1β-primed cells. Moreover, Vanillin determines the increased gene expression of nAChRα7, leading us to hypothesize a role of Vanillin in the activation of the cholinergic anti-inflammatory pathway. Furthermore, in presence of mechanical injury, the Vanillin preincubation, wound closure may be reducing the expression and release of IL-6 and TNF-α and upregulation of COX-2 and IL-8. Conclusion. Together, the results of this study highlight the anti-inflammatory and tissue repair ability of Vanillin in IL-1β-primed HGF. Therefore, Vanillin shows a potential therapeutic interest as an inflammatory modulator molecule with novel application in periodontal regeneration and oral health.
Prediction of Multiple Organ Failure Complicated by Moderately Severe or Severe Acute Pancreatitis Based on Machine Learning: A Multicenter Cohort Study
Background. Multiple organ failure (MOF) may lead to an increased mortality rate of moderately severe (MSAP) or severe acute pancreatitis (SAP). This study is aimed to use machine learning to predict the risk of MOF in the course of disease. Methods. Clinical and laboratory features with significant differences between patients with and without MOF were screened out by univariate analysis. Prediction models were developed for selected features through six machine learning methods. The models were internally validated with a five-fold cross-validation, and a series of optimal feature subsets were generated in corresponding models. A test set was used to evaluate the predictive performance of the six models. Results. 305 (68%) of 455 patients with MSAP or SAP developed MOF. Eighteen features with significant differences between the group with MOF and without it in the training and validation set were used for modeling. Interleukin-6 levels, creatinine levels, and the kinetic time were the three most important features in the optimal feature subsets selected by K-fold cross-validation. The adaptive boosting algorithm (AdaBoost) showed the best predictive performance with the highest AUC value (0.826; 95% confidence interval: 0.740 to 0.888). The sensitivity of AdaBoost (80.49%) and specificity of logistic regression analysis (93.33%) were the best scores among the six models in the test set. Conclusions. A predictive model of MOF complicated by MSAP or SAP was successfully developed based on machine learning. The predictive performance was evaluated by a test set, for which AdaBoost showed a satisfactory predictive performance. The study is registered with the China Clinical Trial Registry (Identifier: ChiCTR1800016079).
Involvement of circRNAs in Proinflammatory Cytokines-Mediated β-Cell Dysfunction
Aim. During the initial stage of type 1 diabetes, prolonged exposure of pancreatic β-cell to proinflammatory cytokines such as IL-1β, TNF-α, and IFN-γ results in a decreased capacity to produce and release insulin, as well as cell loss by apoptosis. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs (ncRNAs) with closed loop with no free ends. circRNAs have been reported to be participated in the development of many diseases. As little is known about their role in insulin-secreting cells, this study is aimed at evaluating their contribution in the process of inflammation-induced β-cell damage. Methods. circRNA expression profile of MIN6 cells stimulated with a mix of cytokines, including IL-1β, IFN-γ, and TNF-α, was detected by circRNA microarrays. Four dysregulated circRNAs were validated by qRT-PCR. The involvement of the selected circRNAs in β-cell dysfunction was tested after their inhibition in MIN6 cells. MicroRNA target prediction software and multiple bioinformatic approaches were used to predict the targeting genes of circRNAs and analyze possible functions of the circRNAs. Results. 1020 upregulated and 902 downregulated circRNAs were identified in cytokines-treated β-cells. Inhibition of circRNAs 000286 and 017277 in β-cells could promote β-cell apoptosis and affect insulin biosynthesis and secretion. GO analysis enriched terms such as regulation of transcription and regulation of gene expression and KEGG analysis enriched top pathways included TGF-β and MAPK signaling pathways. Conclusions. The data shows that circRNAs may be involved in proinflammatory cytokines-mediated β-cell dysfunction and suggests the involvement of circRNAs in the development of type 1 diabetes.
Zataria multiflora and Pioglitazone Affect Systemic Inflammation and Oxidative Stress Induced by Inhaled Paraquat in Rats
The effects of Zataria multiflora (Z. multiflora) and pioglitazone (a PPAR-γ agonist) alone and in combination, on systemic inflammation and oxidative stress induced by inhaled paraquat (PQ) as a herbicide, which induced inflammation in rats, were examined. Rats were exposed to (1) saline (control) and (2) 54 mg/m3 PQ aerosols (8 times, every other day, each time for 30 min) without treatment or treated with (3 and 4) two doses of Z. multiflora (200 and 800 mg/kg/day), (5 and 6) two doses of pioglitazone (5 and 10 mg/kg/day), (7) low doses of , (Pio-5+Z-200 mg/kg/day) or (8) dexamethasone (0.03 mg/kg/day) for 16 days, after the last PQ exposure. Different variables were measured at the end of the treatment period. Exposure to PQ significantly increased total and differential white blood cells (WBC) counts, serum levels of nitrite (NO2), malondialdehyde (MDA), interleukin- (IL) 17, and tumor necrosis factor alpha (TNF-α), but reduced thiol, superoxide dismutase (SOD), catalase (CAT), IL-10, and interferon-gamma (INF-γ) ( to ). Most measured parameters were significantly improved in groups treated with either doses of the extract, pioglitazone, Pio-5+Z-200 mg/kg/day, or dexamethasone compared to the PQ group ( to ). The combination of low doses of Pio-5+Z-200 mg/kg/day showed significantly higher effects compared to each one alone ( to ). Systemic oxidative stress and inflammation due to inhaled PQ were improved by Z. multiflora and pioglitazone. Higher effects of Pio-5+Z-200 mg/kg/day compared to each one alone suggest modulation of PPAR-γ receptors by the plant extract, but further studies using PPAR-γ antagonists need to be done in this regard.
MiR-6869-5p Induces M2 Polarization by Regulating PTPRO in Gestational Diabetes Mellitus
The role of microRNA (miRNA) in gestational diabetes mellitus has been widely investigated during the last decade. However, the altering effect of miR-6869-5p on immunity and placental microenvironment in gestational diabetes mellitus is largely unknown. In our study, the expression of miR-6869-5p was documented to be significantly decreased in placenta-derived mononuclear macrophages, which was also negatively related to PTPRO. Besides, PTPRO was negatively regulated by miR-6869-5p in placenta-derived mononuclear macrophages. In vitro, miR-6869-5p inhibited macrophage proliferation demonstrated by EdU and CCK-8 experiments. The inflammatory response in macrophages was also significantly inhibited by miR-6869-5p, which could regulate PTPRO as a target documented by luciferase reporter assay. Moreover, miR-6869-5p promoted M2 macrophage polarization and thus restrain inflammation. Accordingly, miR-6869-5p is involved in maintaining placental microenvironment balance by preventing from inflammation and inducing M2 macrophages in gestational diabetes mellitus.
Correlation of Low Levels of α-1 Antitrypsin and Elevation of Neutrophil to Lymphocyte Ratio with Higher Mortality in Severe COVID-19 Patients
Background. Variations in COVID-19 prevalence, severity, and mortality rate remain ambiguous. Genetic or individual differences in immune response may be an explanation. Moreover, hyperinflammation and dysregulated immune response are involved in the etiology of severe forms of COVID-19. Therefore, the aim of the present study was to analyze serum alpha-1 antitrypsin (AAT) levels, as an acute-phase plasma protein with immunomodulatory effect and neutrophil to lymphocyte ratio (NLR) as a marker of inflammation response in severe COVID-19 illness. Methods. In this retrospective observational cohort study, 64 polymerase chain reaction (PCR) positive COVID-19 hospitalized patients were studied for AAT, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), troponin, complete blood count (CBC), random blood sugar, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and arterial oxygen saturation (O2sat) at admission and during hospitalization. Results. The results showed that hospitalized patients with COVID-19 had low serum levels of AAT and high CRP levels at the first days of hospitalization. In particular, the percentages of individuals with low, normal, and high AAT levels were 7.80%, 82.80%, and 9.40%, respectively, while high and low values of CRP accounted for 86.70% and 13.30% of patients. Most of the patients had an upward neutrophil to lymphocyte ratio (NLR) trend, with a higher mortality rate () and troponin levels (). However, comorbidities, CRP alterations, ESR alterations, nonfasting blood sugar, SGOT, SGPT, O2sat, RBC, and PLT values were not significantly different between the NLR downward and upward trend groups. Conclusions. The current study revealed that severe COVID-19 patients had low serum AAT levels related to CRP values. Therefore, AAT response may be considered as a new mechanism by which some COVID-19 patients show immune dysregulation and more severe symptoms.