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Background Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery. Methods We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care ( n  = 15) or CytoSorb® HA ( n  = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors’ activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII). Results Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors’ adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes. Conclusions CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts. Trial registration ClinicalTrials.gov NCT02775123 . Registered 17 May 2016.

Background:Increased levels of inflammation have been associated with a poorer response to antidepressants in several clinical samples, but these findings have had been limited by low reproducibility of biomarker assays across laboratories, difficulty in predicting response probability on an individual basis, and unclear molecular mechanisms.Methods: Here we measured absolute mRNA values (a reliable quantitation of number of molecules) of Macrophage Migration Inhibitory Factor and interleukin-1β in a previously published sample from a randomized controlled trial comparing escitalopram vs nortriptyline (GENDEP) as well as in an independent, naturalistic replication sample. We then used linear discriminant analysis to calculate mRNA values cutoffs that best discriminated between responders and nonresponders after 12 weeks of antidepressants. As Macrophage Migration Inhibitory Factor and interleukin-1β might be involved in different pathways, we constructed a protein-protein interaction network by the Search Tool for the Retrieval of Interacting Genes/Proteins. Results:We identified cutoff values for the absolute mRNA measures that accurately predicted response probability on an individual basis, with positive predictive values and specificity for nonresponders of 100% in both samples (negative predictive value=82% to 85%, sensitivity=52% to 61%). Using network analysis, we identified different clusters of targets for these 2 cytokines, with Macrophage Migration Inhibitory Factor interacting predominantly with pathways involved in neurogenesis, neuroplasticity, and cell proliferation, and interleukin-1β interacting predominantly with pathways involved in the inflammasome complex, oxidative stress, and neurodegeneration.Conclusion:We believe that these data provide a clinically suitable approach to the personalization of antidepressant therapy: patients who have absolute mRNA values above the suggested cutoffs could be directed toward earlier access to more assertive antidepressant strategies, including the addition of other antidepressants or antiinflammatory drugs.

To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on serum levels of brain-derived neurotrophic factor (BDNF), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in elderly patients with refractory depression. A total of 58 elderly patients diagnosed with refractory depression between January 2015 and December 2016 were divided randomly into two groups: 29 patients who received rTMS and 29 controls without rTMS. Thirty healthy individuals were also enrolled and all received rTMS. Serum levels of BDNF, IL-1β, and TNF-α were measured before the study (0 days), and at 48 hours and 1, 2, 3, and 4 weeks after the first TMS treatment. BDNF levels gradually increased with treatment duration in the rTMS group and were significantly higher compared with the control group. In contrast, IL-1β and TNF-α levels gradually decreased and were significantly lower than in the control group. None of the serum factors were affected by rTMS in the healthy individuals. BDNF levels were negatively correlated and IL-1β and TNF-α levels were positively correlated with Hamilton Depression Rating Scale-24 scores. These results suggest that rTMS may increase BDNF and decrease IL-1β and TNF-α serum levels in elderly patients with refractory depression.

Background and Objectives: Periodontal inflammation, often linked to oral microbiota dysbiosis dominated by pathogenic bacteria, remains a significant challenge in periodontitis management. Traditional periodontal therapies primarily reduce the bacterial load but fail to restore the microbiota balance. Probiotics offer a promising therapeutic adjunct with their ability to enhance beneficial bacteria. This study investigates the effects of probiotics on the oral microbiota, inflammatory markers (IL-1β, TNF-α), and clinical parameters (gingival index, bleeding index, and periodontal pocket depth). Materials and Methods: In this pilot study, 80 patients with moderate-to-severe periodontitis were assigned to two groups. Group A received standard periodontal therapy (non-surgical periodontal therapy (NSPT)) with probiotic supplementation (Lactobacillus reuteri, 2 × 10⁹ CFU daily for 8 weeks), and Group B received standard treatment with a placebo. Microbiological changes were assessed via quantitative PCR, while inflammatory markers (IL-1β, TNF-α) were analyzed using ELISA. Clinical parameters, including the gingival index (GI), bleeding index (BI), and periodontal pocket depth (PPD), were measured at baseline (T0), 4 weeks (T1), and 8 weeks (T2) using standardized methods. Results: Probiotic therapy (Group A) significantly reduced the pathogenic bacteria and increased the beneficial bacteria levels compared to the placebo (p < 0.01). Inflammatory markers decreased by 37% (IL-1β) and 42% (TNF-α), while clinical parameters improved, with reductions in the gingival and bleeding indices (−1.5, −1.3) and a 2 mm decrease in the periodontal pocket depth (p < 0.01). Conclusions: Probiotics, as an adjunct to periodontal therapy, effectively restore the microbiota balance, reduce inflammation, and improve clinical outcomes in periodontitis.

Background Analyse the effects of Bifidobacterium BB-12 on intestinal metabolites and serum inflammatory factors in premature infants. Methods 71 premature infants at gestational age of ≤32 weeks were randomly divided into the probiotic ( n  = 36) and control ( n  = 35) groups. Faecal and blood samples were collected from the two groups of premature infants at the 2nd and 4th week of life for intestinal metabolite detection and assessment of the level of the serum inflammatory markers TLR4, NF- κ B, IL-1β, and TNF- α. Results Compared to the control group, the probiotic group contained more amino acids, these elements were enriched on multiple amino acid metabolic pathways, and the probiotic group showed significantly lower levels of the serum inflammatory markers TLR4, NF-κB, IL-1β, and TNF-α. Finally, the probiotic group showed a lower incidence of feeding intolerance. Conclusions The administration of Bifidobacterium BB-12 is associated with increasing the levels of glutamine, glutamic acid, and kynurenine in the gut of premature infants, and associated with reducing the levels of TLR4 and NF-κB in the serum, further decreasing the secretion of the pro-inflammatory factors IL-1β and TNF-α, and alleviating systemic inflammatory reactions, thereby reducing the incidence of feeding intolerance. Impact The use of Bifidobacterium BB-12 in premature infants can increase the levels of amino acids in the intestine. Increases in Bifidobacterium BB-12 may decrease the serum levels of TLR4, NF-κB, IL-1β, and TNF-α. Kynurenine may improve the prognosis of preterm infants by reducing inflammation. Bifidobacterium BB-12 may improve the feeding tolerance of premature infants, thus reducing the incidence of feeding intolerance.

Research question In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. Design Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) ‐6, IL‐1β were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. Results A significant decrease in IL-6 and IL-1β concentrations (both, P = < 0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P = 0.01), the MII oocyte count (P = 0.007), oocyte maturity rate (MII %) (P = 0.02) and number of frozen embryos (P = 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. Conclusions AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.

Exercise is an efficacious treatment for major depressive disorder (MDD) and has independently been shown to have anti-inflammatory effects in non-depressed subjects. Patients with MDD have elevated inflammatory cytokines but it is not known if exercise affects inflammation in MDD patients and whether these changes are clinically relevant. In the TReatment with Exercise Augmentation for Depression (TREAD) study, participants who were partial responders to a selective serotonin reuptake inhibitor were randomized to receive one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW), or 4 KKW for 12 weeks. Blood samples were collected before initiation and again at the end of the 12-week exercise intervention. Serum was analyzed using a multiplexed ELISA for interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher baseline levels of TNF-α were associated with greater decrease in depression symptoms over the 12-week exercise period ( P <0.0001). In addition, a significant positive correlation between change in IL-1β and change in depression symptom scores was observed ( P =0.04). There were no significant changes in mean level of any cytokine following the 12-week intervention, and no significant relationship between exercise dose and change in mean cytokine level. Results suggest that high TNF-α may differentially predict better outcomes with exercise treatment as opposed to antidepressant medications for which high TNF-α is linked to poor response. Our results also confirm findings from studies of antidepressant medications that tie decreasing IL-1β to positive depression treatment outcomes.

Knee osteoarthritis (OA) is a prevalent degenerative joint disease globally, causing pain, stiffness, and disability. Intravascular laser irradiation of blood (ILIB) has been used for chronic pain and musculoskeletal disease. However, evidence on the clinical benefits and serum biomarkers post-ILIB therapy in knee OA is insufficient. We designed a double-blind randomized controlled trial to evaluate the clinical and biological outcomes of ILIB therapy for knee OA. Seventeen patients with knee OA were randomly assigned to the ILIB and control groups. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Scale, visual analog scale, and biomarker analysis of interleukin (IL)-6, IL-13, IL-1β, epidermal growth factor, macrophage inflammatory protein-1β, and eotaxin. The measurements were performed at baseline and three days, one month, and three months post-intervention. The ILIB group showed a significant improvement in the WOMAC-pain score at one month of follow-up than the control group. IL-1β levels reduced significantly on day three, one month, and three months, and IL-13 levels reduced on day three and three months during follow-up in the ILIB group. ILIB therapy reduced knee OA pain for one month and significantly reduced serum IL-1β and IL-13 levels, suggesting potential for pain management.

The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group—administered with placebo, and an experimental group—administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.

The aims of this study were to compare circulating cytokines between FM and healthy controls and to investigate the effect on cytokine levels by 15 weeks of progressive resistance exercise or relaxation therapy in FM. Baseline plasma cytokine levels and clinical data were analyzed in 125 women with FM and 130 age-matched healthy women. The FM women were then randomized to progressive resistance exercise (n=49) or relaxation (n=43). Baseline IL-2, IL-6, TNF-α, IP-10, and eotaxin were higher in FM than in healthy controls (P<0.041), whereas IL-1β was lower (P<0.001). There were weak correlations between cytokine levels and clinical variables. After both interventions, IL-1ra had increased (P=0.004), while IL-1β had increased in the relaxation group (P=0.002). Changes of IFN-γ, IL-2, IL-4, IL-6, IL-8, and IL-17A were weakly correlated with changes of PPT, but there were no significant correlations between changes of cytokine and changes in other clinical variables. The elevated plasma levels of several cytokines supports the hypothesis that chronic systemic inflammation may underlie the pathophysiology of FM even if the relation to clinical variables was weak. However, 15 weeks of resistance exercise, as performed in this study, did not show any anti-inflammatory effect on neither FM symptoms nor clinical and functional variables. This trial is registered with ClinicalTrials.gov NCT01226784, registered October 21, 2010. The first patient was recruited October 28, 2010.