Serum Concentrations Of Interleukin-6 Research Articles

Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.

Therapeutic plasma exchange (TPE) is a well-established treatment modality in acute liver failure patients, but its efficacy in treating acute on chronic liver failure (ACLF) patients is yet to be established. To assess the efficacy and safety of TPE in patients with alcohol-associated ACLF who were nonresponders to standard medical treatment (SMT) and without immediate prospects for liver transplantation. Twenty-eight alcohol-related ACLF (grade II) patients (14 cases and 14 controls) were enrolled in the study. Cases underwent standard volume TPE along with SMT while the controls were on SMT alone. The change (baseline to day 10) in laboratory parameters, cytokine concentrations, clinical severity scores along with 30 and 90 day mortality rates were noted and compared between the two groups. The adverse events (AEs) were noted in the groups and analyzed. A total of 51 TPE procedures were performed in 14 patients (average of 3.62 procedures/patient). TPE was effective in reduction of serum bilirubin, ammonia, activated partial thromboplastin time, prothrombin time, international normalized ratio, and severity scores (ACLF Research Consortium, Maddrey's discriminant function, and model for end-stage liver disease) (P < .05). There was no significant difference in the reduction of serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α concentrations among cases. Among the cases who received the complete TPE interventions, 30- and 90-day mortality rates were lower in the cases as compared to controls albeit only the 90-day mortality was significantly different. Procedure-related AEs was observed in 2% of procedures. TPE is an effective and well-tolerated bridge therapy in patients with alcohol-associated ACLF of moderate severity not improving on SMT and without immediate prospects for liver transplantation.

Influences of Antithrombotic Elastic Socks Combined with Air Pressure in Reducing Lower Extremity Deep Venous Thrombosis for Patients Undergoing Cardiothoracic Surgery.

This study was designed to investigate the application and therapeutic effect of antithrombotic elastic socks combined with air pressure in the prevention of lower extremity deep venous thrombosis in patients undergoing cardiothoracic surgery. Sixty patients in cardiothoracic surgery of our hospital from January 2019 to December 2020 were randomly divided into a study group and control group. The control group was treated with routine treatment intervention. Based on routine treatment intervention, the study group was treated with antithrombotic elastic socks combined with pneumatic treatment intervention. The activated partial thromboplastin time (APTT), thrombin time (TT), femoral venous blood flow velocity of both lower limbs, and the incidence of lower extremity deep venous thrombosis (LEDVT), postoperative lower extremity swelling, inflammatory factors, and satisfaction were measured. After intervention, APTT (31.74 ± 1.15 s) and TT (14.58 ± 0.24 s) in the study group were higher than those in the control group APTT (25.13 ± 1.14 s) and TT (12.14 ± 0.23 s) (P < 0.05). The left lower limb femoral vein blood flow velocity and the right lower limb femoral vein blood flow velocity in the study group were better than those in the control group (P < 0.05). The incidence of postoperative lower limb swelling and deep vein in the study group was lower than that in the control group (P < 0.05). Serum tumor necrosis factor alpha and interleukin-6 concentrations in the study group were lower than those in the control group (P < 0.05). The satisfaction rate of patients in the study group (93.33%) was significantly higher than that in the control group (70.00%) (P < 0.05). In conclusion, after cardiothoracic surgery, antithrombotic elastic socks combined with air pressure can significantly reduce the incidence of LEDVT by improving patients' coagulation function, reducing inflammatory reaction. It is worthy of popularization and application in relevant surgery.

The Effect of Adjunctive Probiotics on Markers of Inflammation and Oxidative Stress in Bipolar Disorder: A Double-blind, Randomized, Controlled Trial.

Bipolar disorder (BD) is a chronic psychiatric illness. Concentrations of inflammatory cytokines are increased in BD. Supplementation with probiotics has shown promising effects in reducing inflammation and producing improvement in clinical symptoms in some psychiatric disorders. Therefore, we designed a clinical trial to assess the effects of adjunctive probiotics on markers of inflammation and oxidative stress in patients with BD. In this 8-week, double-blind, randomized study, 38 patients suffering from BD type I were given a probiotic or placebo capsule each day. Serum levels of interleukin-6 (IL-6), as the primary outcome measure, and of interleukin-10 (IL-10), tumor necrosis factor-α, and malondialdehyde, as the secondary outcome measures, were obtained before and after the intervention. At the end of the study, the 2 groups showed no significant or clinically meaningful differences in the serum concentrations of IL-6 [Hedge g=0.02, 95% confidence interval (CI): -0.6; 0.64, P=0.936], tumor necrosis factor-α (Hedge g=-0.2, 95% CI: -0.82; 0.42, P=0.554), IL-10 (Hedge g=-0.072, 95% CI: -0.071; 0.56, P=0.827), and malondialdehyde (Hedge g=0.27, 95% CI: -0.37; 0.91, P=0.423). This study did not find any significant or conclusive effects of probiotics supplementation on markers of inflammation and oxidative stress in patients with BD. Further studies are needed before a conclusion can be drawn about the efficacy of probiotics in the management of BD.

Protective effect of Lindera aggregata on lipopolysaccharide-induced mice acute respiratory distress syndrome by regulating p38MAPK/ERK pathway

To explore the protective effect of Lindera aggregata on acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide (LPS) in mice and its possible mechanism. Forty C57BL/6 mice were randomly divided into sham operation group, ARDS model group, low-dose Lindera aggregata (L-LA) group and high-dose Lindera aggregata (H-LA) group, with 10 mice in each group. ARDS model was established by injecting 5 mg/kg LPS through the trachea. The L-LA group and H-LA group were orally administrated 1 g/kg and 5 g/kg of the Lindera aggregate extract once a day, respectively, while the ARDS model group was given the same volume of normal saline, the sham group received no treatment. The Lindera aggregata was preadministered for 3 days before modeling, and continued for 2 days after modeling, then the animals were sacrificed, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The pathological changes of lung tissue in each group of mice were observed under the microscope and the wet/dry weight ratio (W/D) of the lung were measured. Enzyme linked immunosorbent assay (ELISA) was used to examine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in mice serum and BALF, and flow cytometry was used to detect the expression rate of CD40 on the surface of BALF macrophages. The phosphorylation levels of p38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) proteins in lung tissue were measured by Western blotting. Lung histopathology under light microscope showed that the damage of alveolar structure, thickening of alveolar septum and infiltration of inflammatory cells in the H-LA group were less severe than those in the ARDS model group, while the pathological characteristics of ARDS in the L-LA group were not significantly different from those in the ARDS model group. Compared with the sham operation group, the lung W/D ratio, TNF-α and IL-6 protein contents in serum and BALF, BALF macrophage CD40 expression rate and lung tissue p38 and ERK1/2 protein phosphorylation levels were significantly increased in ARDS model group. The W/D ratio, the concentrations of TNF-α and IL-6 in serum and BALF, the expression rate of CD40 in BALF macrophages, and the phosphorylation levels of p38 and ERK1/2 protein in lung tissue in the L-LA group were not significantly different from those in the ARDS model group. The above indexes in the H-LA group were significantly lower than those in the ARDS model group and the L-LA group [W/D ratio: 5.70±0.19 vs. 6.20±0.31, 6.01±0.17; serum TNF-α (ng/L): 83.63±15.04 vs. 111.75±18.45, 108.12±13.98; serum IL-6 (ng/L): 111.38±8.75 vs. 244.13±26.85, 227.50±9.37; BALF TNF-α (ng/L): 36.25±2.82 vs. 51.13±5.44, 47.50±5.78; BALF IL-6 (ng/L): 35.63±2.20 vs. 49.63±4.90, 46.38±3.50; CD40 expression rate (%): 23.28±2.45 vs. 30.32±2.40, 28.17±1.98; p-p38/p38: 0.50±0.04 vs. 0.74±0.07, 0.69±0.04; p-ERK1/2/ERK1/2: 0.47±0.07 vs. 0.72±0.07, 0.68±0.05; all P < 0.01]. Lindera aggregata can inhibit LPS-induced lung inflammation and alleviate lung injury in ARDS mice. The mechanism may be related to the inhibition of the activation of p38 mitogen activated protein kinase/ERK (p38MAPK/ERK) signaling pathway.

Effects of Dapagliflozin in Combination with Metoprolol Sustained-Release Tablets on Prognosis and Cardiac Function in Patients with Acute Myocardial Infarction after PCI.

Objective To find the effects of dapagliflozin in combination with metoprolol sustained-release tablets on cardiac function and prognosis in acute myocardial infarction patients after PCI. Methods A total of 84 patients with myocardial infarction who experienced PCI from February 2020 to February 2022 were included and allocated into 3 groups: groups A, B, and C (n = 28/per group). Group A was given dapagliflozin combined with metoprolol sustained-release tablets, group B was given dapagliflozin, and group C was given the placebo. Left ventricular end diastolic diameter (EDD), left ventricular ejection fraction (LVEF), and end systolic diameter (ESD) were measured before and after treatment in all groups; myocardial infarction areas were matched among all three groups at 3 months posttreatment. The serum concentrations of interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected in all three groups before and after treatment. The levels of N-terminal probrain natriuretic peptide (NT-pro BNP), lipoprotein (a) (Lp(a)), ischemia-modified albumin (IMA), and secreted frizzled-related protein 5 (SFRP5) were also detected in the serum of all groups. Adverse reactions and cardiovascular adverse events were matched between all groups. Results The levels of LVEF in groups A and B were increased after treatment, while the levels of EDD and ESD were decreased. The improvement degree of LVEF and EDD levels in groups A and B was found greater compared to group C (P < 0.05). No significant difference was found in myocardial infarction area among the three groups at 3 months postoperation (P > 0.05). Serum concentrations of MDA, hs-CRP, IL-6, IMA, NT-proBNP, and Lp(a) were found to decrease in all three groups after treatment, while the levels of SOD and SFRP5 were increased. The improvement degree of serum hs-CRP, IL-6, SOD, MDA, IMA, NT-proBNP, Lp(a), and SFRP5 levels was greater in both groups A and B compared to group C. The improvement degree of serum hS-CRP, SOD, MDA, IMA, Nt-probNP, Lp(a), and SFRP5 levels was significantly greater in group A compared to group B (P < 0.05). No adverse effect was observed in all three groups (P > 0.05). Total occurrence of cardiovascular adverse effects such as stent thrombosis, heart failure, ventricular fibrillation, and death was 10.71% in group A, 25.00% in group B, and 53.75% in group C. There was statistical significance in the onset of cardiovascular adverse effects 3 months postoperation among all three groups (P < 0.05). Conclusion Dapagliflozin with metoprolol sustained-release tablets can be effective in improving the heart function, inflammatory response, oxidative stress response, and prognosis in patients after PCI.

Serum lipids and IL-6 concentration in rats fed with high protein diet after sibutramine treatment

Background and Aims : Diabetes mellitus is a chronic condition characterized by a disturbance in carbohydrates metabolism,fats and proteins. High Protein Diet is associated with a change in carbohydrate metabolism observed in Diabetes. Sibutramine is a nor adrenaline and serotonin reuptake inhibitor that has beneficial effects on serum lipoproteins. Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. Studies in experimental animals indicate that IL-6 in the Central Nervous System partly mediates the suppression of food intake and body weight.

Serum concentrations of interleukin-6 and tumor necrosis factor alpha in patients with spondyloarthritis: a relationship between systemic inflammation and anemia

Aim. To assess the relationship between the activity of systemic inflammation and the hemoglobin level in patients with spondyloarthritis (SpA).Materials and methods. We examined 92 patients with SpA aged 42.9 ± 11.6 years (SpA duration – 14.8 ± 9.6 years, 55 (60%) men). We calculated the BASDAI and ASDAS-CRP scores, performed complete blood count, evaluated erythrocyte sedimentation rate (ESR), ferrokinetic parameters, C-reactive protein (CRP) level, and serum concentrations of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6).Results. Anemia was found in 52 (57%) patients: 13 (25%) patients were diagnosed with anemia of inflammation (AI), 39 (75%) individuals had a combination of AI and iron deficiency anemia. A significant increase in CRP (17.8 vs. 9.0 mg / l, respectively; p = 0.001) and ESR (23 vs. 10 mm / h, p &lt; 0.001), a tendency toward an increase in IL-6 levels (5.4 vs. 4.1 pg / ml, p = 0.051), and no difference in TNF-α levels (3.4 vs. 3.0 pg / ml, p = 0.245) were revealed in patients with anemia compared with patients with normal hemoglobin level. The hemoglobin concentration was negatively correlated with the CRP level (r = –0.327, p = 0.001) and ESR (r = –0.527, p &lt; 0.001). IL-6 was positively correlated with the levels of TNF-a, CRP, and ESR (r = 0.431, r = 0.361, r = 0.369; all p &lt; 0.001). With the IL-6 concentration &gt;10 pg / ml, the odds for anemia were 5.3 times higher (95% confidence interval: 1.4–19.9, p = 0.009).Conclusion. The relationship between the activity of systemic inflammation and anemia in patients with SpA was confirmed. Taking into account the pathogenesis of AI, the aim of antianemic treatment is to achieve remission or minimal activity of SpA. Additional studies are required to determine the effect of anti-inflammatory therapy on the development and course of anemia in patients with SpA.

Fabrication, characterization and application of novel nanoemulsion polyvinyl alcohol/chitosan hybrid incorporated with citral for healing of infected full-thickness wound

Chitosan (Csn) and polyvinyl alcohol (PVA) have mechanical strength properties and can be encapsulated with citral (Cil) into nanoemulsions (NEs) and applied for the treatment of infected wounds. This study investigates the effects PVA/Csn/Cil-NEs for the treatment of infected wounds in a mouse model. The NEs were prepared by the help of Cil, PVA and 10% and 20% Csn. In vitro release and antibacterial properties and also cytotoxicity analysis were done. The therapeutic formulations were prepared and administrated in circular wounds infected with Acinetobacter baumannii and Streptococcus pyogenes. Wound contraction, histopathological parameters total bacterial count, the serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), transforming growth factor-β or (TGF-β), interleukin-10 (IL-10), reactive oxygen species (ROS), and malondialdehyde (MDA), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were evaluated. The NEs were safe and addition of Csn decreased rapid release of Cil. The mice treated with the NEs containing higher concentrations of Csn exhibited lower bacterial count, the serum concentrations of TNF-α, IL-1β, ROS, MDA, edema, and immune cells and higher the serum concentrations of TGF-β and IL-10, activities SOD and GPx, and collagen deposition. In conclusion, the PVA/Csn/Cil-NEs expedited infected wounds in a mice model.

Study on the concentration of serum interleukin-6 in rheumatoid arthritis patients

Background: Helper T lymphocytes 17 (Th17) secrete various interleukins, including Interleukin-6 (IL-6), which promotes the pathological process in rheumatoid arthritis patients. Therefore, serum Interleukin-6 levels may be related to the clinical and subclinical characteristics of rheumatoid arthritis. Objectives: To determine serum Interleukin-6 concentrations in rheumatoid arthritis patients and to investigate the relationship between serum Interleukin-6 concentration with some clinical and subclinical characteristics in patients with rheumatoid arthritis. Subjects and method: A cross-sectional descriptive study of 41 patients with rheumatoid arthritis in Hue University of Medicine and Pharmacy hospital and 30 healthy people in a control group. Results: The mean serum IL-6 concentration of the patient group was 120.57 pg/mL which was statistically significantly higher (p &lt; 0.001) than the control group (5.73 pg/mL). There was a statistically significant positive correlation (p &lt; 0.05) between serum Interleukin-6 concentration and the time of disease onset, the number of damaged joints and the 2nd-hour erythrocyte sediment rate. There was a statistically significant inverse correlation (p &lt; 0.05) between serum Interleukin-6 concentration with red blood cell amount, hemoglobin concentration. There was a statistically significant relationship (p &lt; 0.05) between serum Interleukin-6 concentration and CRP, RF, Anti-CCP and 1st-hour erythrocyte sediment rate. Conclusion: Increased serum IL-6 levels in rheumatoid arthritis patients affect joint injury, induce anemia, promote inflammation and increase autoantibodies. Key words: Interleukin-6, Rheumatoid Arthritis.

Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage: A prospective case control study.

BACKGROUNDBiliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually. Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality, it is important to identify factors and mechanisms involved in its development.AIMTo determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status.METHODSThis was a prospective case control study performed in a tertiary center in Zagreb, Croatia. Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled. After excluding patients who developed procedure related complications or were lost in the follow-up, out of initial 73 patients, 55 patients were included in the analysis, including 34 with benign and 21 with malignant disease. Meanwhile, 40 non-jaundiced controls were also included. Appetite, nutritional status, and serum ghrelin, cholecystokinin (CCK), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were determined at admission, 48 h and 28 d after internal biliary drainage. Chi square test was used for categorical variables. Continuous variables were analysed for normality by Kolmogorov–Smirnov test and relevant non-parametric (Mann-Whitney, Kruskal-Wallis, and Friedman) or parametric (t-test and analysis of variance) tests were used.RESULTSPatients with obstructive jaundice were significantly malnourished compared to controls, regardless of disease etiology. Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice. Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α, but had no correlation with CCK concentrations. After internal biliary drainage, a significant improvement of nutritional status was observed although serum concentrations of ghrelin, IL-6, and TNF-α remained significantly elevated even 28 d after the procedure. CCK levels in patients without malnutrition remained elevated 28 d after the procedure, but in patients with malnutrition, CCK levels decreased to levels comparable with those in the control group. We have not established any correlation between appetite and serum levels of ghrelin, CCK, IL-6, and TNF-α before and after biliary drainage.CONCLUSIONPossible abnormalities in ghrelin and CCK regulation may be associated with the development of malnutrition during the inflammatory response in patients with biliary obstruction.

Abstract CT119: A randomized, double-blind phase 2 evaluation of the anti-IL-8 monoclonal antibody BMS-986253 + nivolumab + ipilimumab vs nivolumab + ipilimumab in patients with advanced melanoma that progressed on/after anti-PD-(L)1 therapy

Abstract Purpose: This phase 1/2 trial evaluates the novel immunotherapy BMS-986253 in combination with immune checkpoint inhibitors (NCT03400332). Interleukin-8 (IL-8) is an immunosuppressive chemokine often elevated in the serum of patients with cancer. High serum IL-8 concentration is associated with poor prognoses and resistance to immunotherapies, including anti-programmed death-1 (PD-1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents (Schalper et al. Nat Med 2020;26:688). The addition of anti-IL-8 therapy to anti-PD-1 nivolumab (NIVO) and anti-CTLA-4 ipilimumab (IPI) may sensitize patients with high serum IL-8 levels to immune checkpoint inhibition. BMS-986253, a fully human IgG1 anti-IL-8 monoclonal antibody, in combination with NIVO ± IPI is under investigation in a phase 1/2 trial of patients with advanced solid tumors. Initial results from part 1 indicate BMS-986253 + NIVO was well tolerated with no dose-limiting toxicities (Davar et al. J Immunother Cancer 2020;8. Abstract 394). Preliminary antitumor activity was observed, including partial responses in 5 of 28 patients with melanoma that had progressed on or after prior anti-PD-(L)1 therapy, a population with high unmet medical need. Part 2 is a randomized, double-blind phase 2 study comparing the efficacy of BMS-986253 in combination with NIVO + IPI vs NIVO + IPI in patients with advanced melanoma that progressed on or after prior anti-PD-(L)1 therapy. Trial Design: Patients eligible for part 2 have histologically confirmed, unresectable, stage III/IV melanoma, have progressed on or after anti-PD-(L)1 treatment, had an anti-PD-(L)1 agent as their most recent therapy, and have not received anti-CTLA-4 treatment. PD-L1 and BRAFV600 mutation status (wild-type and BRAF mutations permitted) must be documented, and serum IL-8 levels will be measured at screening. Patients will be randomized 1:1 to receive BMS-986253 + NIVO + IPI or placebo + NIVO + IPI and stratified by serum IL-8 level, BRAF V600E status, and lactate dehydrogenase level. The dose and frequency of BMS-986253, NIVO, and IPI will be determined by part 1 data. Treatment with BMS-986253 or placebo and NIVO will continue ≤ 3 years or until disease progression or intolerance. The primary objective is to compare progression-free survival (PFS) by blinded independent central review (BICR) per RECIST v1.1 between treatment arms in patients with baseline serum IL-8 levels &amp;gt; 10 pg/mL. Secondary objectives include PFS by BICR in all randomized patients, overall response rates by BICR per RECIST v1.1, overall survival, safety, pharmacokinetic profile, immunogenicity of BMS-986253, and associations of baseline factors with response. Recruitment will continue until ≈170 patients are enrolled. Citation Format: Matteo Simonelli, Emiliano Calvo, Diwakar Davar, Jason Melear, Donald Richards, Matthew Dallos, Martin Gutierrez, Victor Moreno, Thomas Marron, Sylvie Rottey, Angela Orcurto, Susana Barriga, Jessy Fan, Elizabeth Gibson, Santanu Dutta, Vivek Arora, Ignacio Melero. A randomized, double-blind phase 2 evaluation of the anti-IL-8 monoclonal antibody BMS-986253 + nivolumab + ipilimumab vs nivolumab + ipilimumab in patients with advanced melanoma that progressed on/after anti-PD-(L)1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT119.

Comparative Efficacy of Fish Meal Replacement With Enzymatically Treated Soybean Meal on Growth Performance, Immunity, Oxidative Capacity and Fecal Microbiota in Weaned Pigs.

This study investigated the growth performance, immunity, antioxidant capacity and fecal microbiota of weaned pigs by partially or completely replacing dietary fish meal with enzymatically treated soybean meal. A total of 144 piglets (initial body weight of 7.19 ± 0.11 kg) weaned at 28 d were allotted to 3 dietary treatments (6 replicates per treatment): 4% fish meal diet (FM); 2% fishmeal plus 6% enzymatically treated soybean meal (ESBM1); and 6% enzymatically treated soybean meal without fish meal (ESBM2). The experimental period was 28 d, serum was collected at day 14 and day 28 for biochemical parameters analysis, feces was obtained for microbiota analysis at 28d. The body weight, average daily gain and average daily feed intake of piglets in the ESBM2 group were significantly increased compared with those in the FM and ESBM1 groups from 0 to 28 d, respectively (P < 0.05). The diets with enzymatically treated soybean meal in ESBM1 and ESBM2 groups decreased the diarrhea rate (P < 0.05). Compared with FM, ESBM1 and ESBM2 decreased 5-hydroxytryptamine (5-HT) (P < 0.05). ESBM1 decreased diamine oxidase (DAO) and Interleukin 6 (IL-6) compared with FM and ESBM2 (P < 0.05). ESBM1 decreased serum Interleukin 1β (IL-1β) compared with FM at d 14 (P < 0.05). The serum Immunoglobulin E (IgE), secretory curl associated protein 5 (sFRP-5) were higher in ESBM1 compared with FM and ESBM2 (P < 0.05). ESBM2 increased super oxidase dismutase (SOD) level and decreased malondialdehyde (MDA) content compared with FM and ESBM1, the concentration of SOD in ESBM1was higher than that in FM (P < 0.05). ESBM1 decreased cortisol and caspase 3 (Casp-3) (P < 0.05). FM showed a higher content of tri-iodothyronine (T3) (P < 0.05) and a lower thyroxine/ tri-iodothyronine ratio compared with those in the other two groups (P < 0.05). The concentration of leptin was lower in ESBM2 (P < 0.05). ESBM1 had a higher α-diversity than ESBM2 (P < 0.05). The microbiota composition was different among three treatments (difference between FM and ESBM1, p = 0.005; FM and ESBM2, p = 0.009; ESBM1 and ESBM2, p = 0.004). ESBM2 tend to increase the abundance of Firmicutes (P = 0.070) and decrease Bacteroidetes (P = 0.069). ESBM2 decreased the abundance of Parabacteroides and increased SMB53 compared with FM (P < 0.05). The spearman correlation analysis revealed that the abundance of Parabacteroides enriched in FM group was negatively correlated with SOD, Megasphaera enriched in ESBM2 group were positively correlated with SOD. The abundance of Lachnospira enriched in ESBM2 group were negatively correlated with serum concentration of D-lactate, DAO, IL-6, and NO. In conclusion, under the conditions of this study, diet with only ESBM demonstrate the beneficial impact on intestinal microbiota developments, antioxidant capacity as well as growth performance for weaned pigs.

Effect of bortezomib on fatty liver in a rat model of atherosclerosis

Introduction and Aim: Fatty liver is associated with atherosclerosis even though the exact mechanism remains unknown. Fatty liver and atherosclerosis correlate with inflammation. Interleukin 6 (IL-6) is recognized as an inflammatory marker. Bortezomib is a proteasome inhibitor that will inhibit the proteasome pathway and is expected to inhibit inflammation in atherosclerosis. The current research aimed to investigate the effect of bortezomib on the fatty liver of atherosclerosis rats and to analyze its correlation with serum IL-6 concentration. Materials and Methods: Experimental subjects were 18 male Wistar rats (Rattus novergicus) divided into three treatment groups, namely atherosclerosis group (I), atherosclerosis + bortezomib group (II), and control group (III). Bortezomib (50 ?g/kg BW) was given twice intraperitoneally, on day 1 and day 3. The presence of fatty liver was evaluated using the percentage system. Serum IL-6 concentrations were measured using enzyme-linked immunosorbent assay kits. Results: The highest amount of fatty liver was found in the atherosclerosis group (group I) (38.33%), while the lowest was in the control group (group III) (5.83%). There was a decreasing fatty liver percentage due to bortezomib administration (group II) (29.17%), and it was statistically significant. There is a significant correlation between the degree of fatty liver and serum IL-6 concentration. Conclusion: The administration of bortezomib 50 ?g/kg BW in atherosclerosis model rats can reduce the occurrence of fatty liver by reducing the inflammatory process.

Atopy manifestations in pediatric patients with acute lymphoblastic leukemia: correlation assessment with interleukin-4 (IL-4) and IgE level

BackgroundAcute lymphoblastic leukemia (ALL) is the most common type of cancer in the age range of under 15 years old and accounts for 25–30% of all childhood cancers. Although conventional chemotherapy regimens are used to improve the overall survival rate, it has been associated with some complications, amongst which allergic manifestations with unknown mechanisms are more common.MethodsOur study compared serum IgE and IL-4 concentration, as a hallmark of allergic responses in pediatric ALL patients before and after 6 months of intensive (high-dose) chemotherapy, to show whether changes in the level of these markers may be associated with atopy. Serum level of IL-4 and IgE was measured using enzyme-linked immunosorbent assay (ELISA) method.ResultsThe results showed that the level of IgE and IL-4 increased following chemotherapy in both ALL patients with and without atopy. In addition, post-chemotherapy treatment IgE and IL-4 levels were significantly elevated in patients with atopy compared to those without it. The difference between baseline and post-chemotherapy level of IgE and IL-4 was significantly higher in patients with atopy compared to those without it.ConclusionsTo the best of our knowledge, this is the first study that showed a connection between post-chemotherapy allergic manifestations in pediatric ALL patients and IL-4 and IgE level. Flow cytometry analysis of the T-helper 2 (Th2) lymphocytes and other allergy-related T cell subsets like Tc2 and Th9 as well as the study of the genetic variations in atopy-related genes like IL-4/IL-4R, IL-5, IL-9, IL-13, and high affinity FcεRI IgE receptor and also HLA genes is necessary to clearly define the underlying mechanism responsible for post-chemotherapy hypersensitivity reaction in pediatric ALL patients.

Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans: In vivo and in vitro evidence.

We investigated whether 20 candidate single nucleotide polymorphisms (SNPs) were associated with in vivo exercise-induced muscle damage (EIMD), and with an in vitro skeletal muscle stem cell wound healing assay. Sixty-five young, untrained Caucasian adults performed 120 maximal eccentric knee-extensions on an isokinetic dynamometer to induce EIMD. Maximal voluntary isometric/isokinetic knee-extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity and interleukin-6 concentration were assessed before, directly after and 48 h after EIMD. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12), and markers of repair were measured in vitro. Participants were genotyped for all 20 SNPs using real-time PCR. Seven SNPs were associated with the response to EIMD, and these were used to calculate a total genotype score, which enabled participants to be segregated into three polygenic groups: 'preferential' (more 'protective' alleles), 'moderate', and 'non-preferential'. The non-preferential group was consistently weaker than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N ∙ m/kg; P = 9.51 × 10-4 ) and demonstrated more muscle soreness (p = 0.011) and a larger decrease in knee joint ROM (p = 0.006) following EIMD. Two TTN-AS1 SNPs in linkage disequilibrium were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated muscle stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006). Thus, we have identified a polygenic profile, linked with both muscle weakness and poorer recovery following EIMD. Moreover, we provide evidence for a novel TTN gene-cell-skeletal muscle mechanism that may help explain some of the interindividual variability in the response to EIMD.

Bee Venom Within Liposomes Synergistically Inhibit Atopic Dermatitis in Mice

Background: This study was performed to determine the effects of liposome-encapsulated bee venom (BV) treatment of inflammatory factors in atopic dermatitis (AD) compared with BV treatment.Methods: AD was induced by phthalic anhydride in mice and the effects of BV liposomes were measured. Using Leica Application Suite, thickened epidermis and dermis were measured after BV liposome treatment (0.05 and 0.1 μg/mL). The number of stained mast cells and the concentration of immunoglobulin (Ig)E were measured. Serum IgE concentration was analyzed using an enzyme-linked immunosorbent assay. The serum concentrations of interleukin (IL)-1, IL-4, and IL-6 inflammatory cytokines were measured. The levels of messenger ribonucleic acid expression of proinflammatory cytokines and chemokines were measured using reverse transcription polymerase chain reaction. Inhibition of mitogen-activated protein kinase activation, was analyzed on western blot. To measure the transcriptional activity (NF-κB inhibition by BV liposomes), western blots (p65, p-IκB, p50, and IκB) were also performed.Results: The weight of lymph nodes, serum IgE concentrations, morphological changes in the skins from the backs of the mice, and mast cell numbers in inflamed tissues were noticeably lower in the BV liposome treatment group compared with the BV treatment group. The concentrations of pro-inflammatory cytokines (IL-1, IL-4, IL-6) and chemokines (TSLP, CCL22) were also reduced. Activation of mitogen-activated protein kinase (p-ERK and p-p38), and transcriptional activity (p65, p-IκB, p50, and IκB) was strongly suppressed in the BV liposome group.Conclusion: BV liposomes may have a better therapeutic effect than BV for the treatment of AD.

Predictive Value of B reg and Serum IL-10 Concentration Levels for Acute ITP Progression to Chronic Phase.

Pediatric immune thrombocytopenia (ITP) is a potentially life threating autoimmune disorder with different responses to therapy and different bleeding phenotypes in critical organs. The molecular basis for the variable response has not yet been fully elucidated. This study was designed to address the predictive value of regulatory B-cell (B reg ) count and interleukin-10 (IL-10) serum levels for acute ITP patients who progress to chronic phase. The present study included 80 children with acute ITP )38 males and 42 females (with median age of 8 years and 40 matched healthy controls. Assessment of B reg (CD19 + CD24 hi CD38 hi ) was carried out by a multicolor flowcytometry, however, IL-10 serum levels were evaluated by enzyme-linked immunosorbent assay. A significant reduction of B reg percentage and a significant increase in serum IL-10 levels were identified in children with acute ITP as compared with controls ( P <0.001 for both). Fourteen ITP patients passed to chronic phase, while 66 patients achieved remission within 6 months. The absolute B reg was significantly lower, while IL-10 was significantly higher in patients with acute ITP who progressed to chronic phase in comparison with acute ITP patients who achieved complete remission. Cox proportional hazards for ITP chronicity revealed that IL-10 OR was 2.46 (confidence interval: 1.42-4.27; P =0.001) and absolute B reg OR was 0.147 (confidence interval: 0.128-0.624; P =0.005) in the peripheral blood. Therefore, they could predict chronicity in ITP cases. Reduced B reg count and elevated IL-10 levels in patients with acute ITP at diagnosis can predict chronicity.

Interleukin-26 is associated with the level of systemic inflammation and lung functions in obese and non-obese moderate-to-severe asthmatic patients.

Obese asthma is a complex syndrome, which includes different phenotypes of disease. At present, these phenotypes only have started to acquire a sufficient understanding. It was suggested that IL-26 is a potential biomarker of disease severity in asthma without signs of Th2-mediated inflammation. In this study, we investigated the serum and exhaled levels of IL-26 and its associations with the level of systemic inflammation, lung functions, and body weight in obese and non-obese moderate-to-severe asthmatic patients MATERIAL AND METHODS: The study included 10 healthy subjects, 10 obese subjects without lung pathologies, 10 non-obese asthmatics (NOA) (BMI 18.5-24.9 kg/m²), and 40 obese asthmatics (OA) (BMI 25.0-49.9 kg/m²). During the visit, patients' examination and spirometry with the bronchodilator reversibility test were conducted, the exhaled breath condensate (EBC) was obtained, and the blood samples were collected. The level of IL-26, interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), TNF-α, interleukin-10 (IL-10), total and specific immunoglobulin E (IgE), and high sensitive C reactive protein (hs-CRP) were measured using the ELISA kits. Statistical comparison between 2 groups was analyzed using the Mann-Whitney rank-sum test. Chi-square with Yates' correction was used to compare frequencies. Spearman's rank test was used for correlating nonparametric variables. The Receiver Operating Characteristic (ROC) curve and the area under ROC curve (AUC) were used for evaluating the diagnostic power of IL-26 as a possible biomarker. NOA had a reversible airway obstruction with reduced FEV1, FEV1/FVC, FVC 25/75, and positive post-bronchodilator test (PBT), significantly increased serum levels of IL-10, IL-4, and slightly increased IL-26. NOA had significantly increased exhaled IL-26 in comparison with healthy subjects. The obese subjects had a normal ventilatory pattern without airway obstruction, and differences in serum IL-26, IL-10, and IL-4 concentrations in comparison with healthy subjects. Obese subjects had a significant escalation of hs-CRP and no differences in the levels of exhaled IL-26, IL-10, and hs-CRP as compared with healthy subjects. OA had reduced FEV1, FEV1/FVC, and FEV25-75 in comparison with non-obese asthmatics. OA had elevated IL-26, IL-10, IL-4, and hs-CRP concentrations as compared with healthy subjects. These patients had a partial similarity with both non-obese asthmatics (elevated IL-26, IL-10, and IL-4) and obese subjects (elevated, IL-1β, IL-6, TNF-α, hs-CRP). OA had a reduced concentration of exhaled IL-26 in comparison with NOA and elevated exhaled IL-10 in comparison with obese subjects. Furthermore, OA had an increased concentration of IL-1β and TNF-α in comparison with healthy individuals and NOA. Exhaled IL-26 concentration distinguished non-obese asthmatics from healthy subjects, asthmatic patients from non-asthmatics (healthy and obese subjects), all asthmatic patients from non-asthmatics (healthy and obese subjects). Exhaled IL-26 elevated in obese and non-obese moderate-to-severe asthmatic patients. Exhaled IL-26 might be a perspective biomarker in non-obese and obese asthmatics. The obese asthmatic phenotype comprised the combined systemic and local airway inflammation.

An 18-hole round of golf acutely elevates serum interleukin-6 and brain-derived neurotrophic factor concentration - a pilot study

An 18-hole round of golf acutely elevates serum interleukin-6 and brain-derived neurotrophic factor concentration - a pilot study

Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial

BackgroundIn acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients’ individual response is warranted.End-expiratory lung volume (EELV) assessment by nitrogen washin-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient’s individual recruitability.We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial).MethodsIPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O.To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP).Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28–30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized.The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment.DiscussionThe IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS.Trial registrationClinicalTrials.govNCT04012073. Registered 9 July 2019.