Comparative Effectiveness of Anti-Inflammatory Drug Treatments in Coronary Heart Disease Patients: A Systematic Review and Network Meta-AnalysisRead 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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Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement
Background and Objectives. Tourniquet-induced ischemia/reperfusion (I/R) injury is a common clinical problem for patients receiving surgery. The objective of this study is to determine if oxycodone (Oxy) reduces skeletal muscle I/R damage induced by tourniquet placement and explores the underlying mechanisms. Method. Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-κB, SIRT1, and PGC-1α in the skeletal muscles were detected by western blot. Blood TNF-α levels, gastrocnemius muscle contractile force, and ATP concentration were examined. Results. Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF-α levels, and inhibited the expression levels of TLR4/NF-κB in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels. Conclusion. Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-κB-dependent inflammatory response and protects SIRT1/PGC-1α-dependent mitochondrial function.
The Relationship between Retinol-Binding Protein 4 and Markers of Inflammation and Thrombogenesis in Children with Kawasaki Disease
Background. Kawasaki disease (KD) is a self-limited vasculitis with unknown etiologies, and coronary artery lesions (CALs) are the most common and serious complications. Retinol-binding protein 4 (RBP4) has been confirmed effects on vasodilation, platelet activation inhibition, and cardiovascular diseases by researches. Therefore, this study was aimed at investigating the relationship between RBP4 and inflammation as well as thrombogenesis in children with KD. Methods. 79 subjects were from 62 children with KD and 17 healthy controls (HCs). The KD group was divided into KD with CALs (KD-CALs) and KD without CALs (KD-NCALs), and the serum RBP4 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results. Compared with the HC group, serum RBP4 levels in the KD group were significantly decreased (). RBP4, hemoglobin (Hb), and mean platelet volume (MPV) levels were higher, while platelet counts (Plt) and thrombin time (TT) levels were lower in the KD-NCALs group than in the KD-CALs group (). RBP4 had positive correlation with time point of intravenous immunoglobulin (IVIG), Hb, and percentage of leukomonocytes (L%) and negative correlation with the percentage of neutrophils (N%), MPV, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), prothrombin time (PT), fibrinogen (Fbg), and D-dimer (DD) in the KD group; RBP4 had positive correlation with the time point of IVIG and L% and negative correlation with N%, MPV, and NLR in the KD-NCALs group; and RBP4 had positive correlation with Hb and L% and negative correlation with N%, CRP, NLR, and PT in the KD-CALs group (). Multiple linear regression analysis confirmed that Hb and CRP in the KD group, MPV and N% in the KD-NCALs group, and PT and CRP in the KD-CALs group were independent predictors of RBP4 (). Conclusion. Lower RBP4 was observed in the KD group than in the HC group, and RBP4 had associations with markers of inflammation and thrombogenesis in children with KD.
Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients
Introduction. Intra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma. Materials and Methods. In this cross-sectional study, synovial fluid (SF) and plasma of forty-seven patients with acute intra-articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank-sum and Spearman tests were used for statistical analysis, and a value below 0.05 was considered significant. Results. Compared to the healthy ankles, the synovial fluid in ankles with acute intra-articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL-1β, IL-2, IL-6, IL-8, IL-12p70, TNF, IFNγ, MMP-1, MMP-3, and MMP-9) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, and IL-13). The levels of cartilage degradation products (ACG, CTX-2) and metabolic mediators (TGF-β1 and TGF-β2) were also significantly higher. Synovial concentrations of ACG, IL-12-p70, IFNγ, IL-4, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL-4 and IL-6 levels were upregulated. Conclusions. We show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross-sectional study was “retrospectively registered” on the 31th October 2017 at ClinicalTrials.gov (NCT03769909). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses: https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1.
Effect of Oral Administration with Lactobacillus plantarum CAM6 Strain on Sows during Gestation-Lactation and the Derived Impact on Their Progeny Performance
Background. To evaluate the biological response of the sows and their offspring with oral administration of Lactobacillus plantarum CAM6 in breeding sows, a total of 20 Pietrain breeding sows with three farrowings and their descendants were used, randomly divided into two groups of 10 sows each. Treatments included a basal diet (T0) and basal diet +10 mL biological agent containing 109 CFU/mL L. plantarum CAM6 (T1). No antibiotics were used throughout the entire experimental process of this study. Results. The L. Plantarum CAM6 supplementation in sows’ feeding did not affect () the reproductive performance of the sows; however, the number of deaths for their offspring before weaning () decreased. In addition, the oral administration of Lactobacillus plantarum CAM6 in sows increased () the content of lactose, nonfat solids, mineral salts, and the density of sows’ milk, with a decrease in milk fat. Moreover, the probiotic feed orally to the sows improved the body weight () and reduced the diarrhea incidence of their offspring (). Also, the probiotic administration of sows changed () the serum concentration of Na+, pCO2, and D-β-hydroxybutyrate and increased () the leukocytes, lymphocytes, and platelets in their piglets. Conclusion. Oral administration of Lactobacillus plantarum CAM6 in breeding sows improved body weight, physiological status, and the health of their offspring. And preparing the neonatal piglets physiologically is of great importance to the pig farming industry which could decrease the operational cost and medication (especially antibiotics) consumption of the pig producers.
MicroRNA-155: Regulation of Immune Cells in Sepsis
MicroRNAs are small noncoding RNAs which regulate gene expression at the posttranscriptional level. miR-155 is encoded by the miR-155 host gene (miR155HG), also known as the noncoding B cell integration cluster (BIC). MicroRNAs are widely expressed in various hematopoietic cells and are involved in regulating the immune system. In this review, we summarized how miR-155 modulates specific immune cells and the regulatory role of miR-155 in sepsis. miR-155 is expressed by different populations of innate and adaptive immune cells and is involved in the regulation of development, proliferation, and function in these cells. Sepsis is associated with uncontrollable inflammatory responses, accompanied by unacceptably high mortality. Due to the inadequacy of diagnostic markers as well as treatment strategies, treating sepsis can be a huge challenge. So far, a large number of experiments have shown that the expression of miR-155 is increased at an early stage of sepsis and that this increase is positively correlated with disease progression and severity. In addition, by blocking the proinflammatory effects of miR-155, it can effectively improve sepsis-related organ injury, providing novel insights to identify potential biomarkers and therapeutic targets for sepsis. However, since most of the current research is limited to animal experiments, further clinical research is required to determine the function of miR-155 and its mechanism related to sepsis.
Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids
Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.