Molybdenum disulfide-gold nanoparticle nanocomposite in field-effect transistor back-gate for enhanced C-reactive protein detection.

Nanofabricated gold nanoparticles (Au-NPs) on MoS2 nanosheets (Au-NPs/MoS2) in back-gated field-effect transistor (BG-FET) are presented, which acts as an efficient semiconductor device for detecting a low concentration of C-reactive protein (C-RP). The decorated nanomaterials lead to an enhanced electron conduction layer on a 100-µm-sized transducing channel. The sensing surface was characterized by Raman spectroscopy, ultraviolet-visible spectroscopy (UV-Vis), atomic force microscopy (AFM), scanning electron microscopy (SEM), and high-power microscopy (HPM). The BG-FET device exhibits an excellent limit of detection of 8.38 fg/mL and a sensitivity of 176 nA/g·mL-1. The current study with Au-NPs/MoS2 BG-FET displays a new potential biosensing technology; especially for integration into complementary metal oxide (CMOS) technology for hand-held future device application.

The effects of omega-3 fatty acid supplementation on inflammatory factors in HIV-infected patients: A systematic review and meta-analysis of randomized clinical trials.

High concentrations of C-reactive protein (CRP) and inflammatory markers are common in human immunodeficiency virus (HIV)-infected patients and are associated with non-HIV related comorbidity and mortality. Data on the benefits of omega-3 fatty acid (omega-3 FA) supplementation for improving inflammation status in HIV-infected patients are controversial. Thus, we conducted a systematic review and meta-analysis on the beneficial effects of omega-3 FAs on controlling inflammation in HIV-infected patients. We conducted a comprehensive search of the major biomedical databases, including PubMed, EMBASE, Scopus, Web of Science and Cochrane library, for all potentially relevant studies published without restriction from the beginning of time to June 2020. Overall, nine RCTs were included comprising a total of 427 participants. A random-effects model was used to calculate 95% confidence intervals (CI) and the effect was measured as standardized mean difference (SMD). Supplementation of omega-3 FAs showed a significant reduction of CRP (SMD: -0.27, 95% CI: -0.48 to -0.07, P = 0.007). There was no significant difference in levels of TNF-α (SMD: 0.03, 95% CI: -0.79 to 0.85, P = 0.94, I2 = 87%) and IL-6 (SMD: -0.13, 95% CI: -0.59 to 0.32, P = 0.57, I2 = 73%, Fig. 3). The results indicate that the supplementation of omega-3 FAs in HIV-infected patients significantly decreases serum CRP levels when compared to the control group, however has no significant effect on IL-6 and TNF-α levels.

Efficacy of Rebixiao Chinese herbal tablets and Chinese formula granules in acute gout arthritis patients: a randomized, multicenter, double-blind, controlled trial.

OBJECTIVE: To evaluate the clinical efficacy and safety of Rebixiao (RBX) Chinese herbal tablets (CHT) and Chinese formula granules (CFG) in the treatment of acute gout arthritis (AGA). METHODS: This randomized, multicenter, double-blind, controlled trial included 165 AGA patients with the damp-heat symptom pattern who were randomly divided into an RBX CHT group and an RBX CFG group and treated for 7 d at three centers. The total effective rates of the joint symptom score, Traditional Chinese Medicine (TCM) symptoms score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were used to evaluate the clinical efficacy. Safety assessments were also performed. RESULTS: Of the 165 enrolled patients, 147 completed the clinical observation. There was no difference in baseline between the two groups. The total effective rates of the joint symptom score were 94.36% and 97.36%, and the total effective rates of the TCM symptoms score were 95.77% and 97.36% in the CFG group and CHT group, respectively. No statistical difference was found between the two groups (P > 0.05). Additionally, ESR and CRP were similar in both groups (P > 0.05). Furthermore, treatment efficacy regarding TCM and joint symptoms, the ESR, and CRP were consistent within each center and among the different centers (P > 0.05). In addition, the incidence of adverse events was 4.22% and 2.63% in the CFG group and CHT group, respectively, and no difference was observed between the two groups (P > 0.05). CONCLUSION: RBX CFG and CHT have significant and similar efficacy in the treatment of AGA, and CFG did not increase adverse side effects.

Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA)-a randomized, controlled crossover trial indicating effects on disease activity.

BACKGROUND: Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on clinical outcomes in RA, but insufficient evidence exists to provide specific dietary advice. Food components may interact but studies evaluating combined effects are lacking. OBJECTIVES: We aimed to investigate if an anti-inflammatory diet reduces disease activity in patients with RA. METHODS: In this single-blinded crossover trial, 50 patients with RA were randomly assigned to an intervention diet containing a portfolio of suggested anti-inflammatory foods, or a control diet similar to the general dietary intake in Sweden, for 10 wk. After a 4-mo washout period the participants switched diet. Food equivalent to ∼50% of energy requirements was delivered weekly to their homes. For the remaining meals, they were encouraged to consume the same type of foods as the ones provided during each diet. Primary outcome was change in Disease Activity Score in 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR). Secondary outcomes were changes in the components of DAS28-ESR (tender and swollen joints, ESR, and visual analog scale for general health) and DAS28-C-reactive protein. RESULTS: In the main analysis, a linear mixed ANCOVA model including the 47 participants completing ≥1 diet period, there was no significant difference in DAS28-ESR between the intervention and control periods (P = 0.116). However, in unadjusted analyses, DAS28-ESR significantly decreased during the intervention period and was significantly lower after the intervention than after the control period in the participants who completed both periods (n = 44; median: 3.05; IQR: 2.41, 3.79 compared with median: 3.27; IQR: 2.69, 4.28; P = 0.04, Wilcoxon's Signed Rank test). No significant differences in the components were observed. CONCLUSIONS: This trial indicates positive effects of a proposed anti-inflammatory diet on disease activity in patients with RA. Additional studies are required to determine if this diet can cause clinically relevant improvements.This trial was registered at clinicaltrials.gov as NCT02941055.

The Impact of Pre-Cooling and CoQ10 Supplementation on Mediators of Inflammatory Cytokines in Elite Swimmers.

Chronic intensive exercise and hyperthermia may cause immune system function disturbance. We aimed to investigate the effect of 14-day coenzyme Q10 (CoQ10) supplementation and pre-cooling strategy on serum changes of inflammatory cytokines [interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)], and high-sensitivity C-reactive protein (hs-CRP), myeloperoxidase (MPO) and xanthine oxidase (XO) enzymes, leukocyte counts (WBC), and stress hormones (catecholamine and cortisol) responses in elite swimmers during competition phase. Thirty-six healthy males were randomly selected and divided into four groups of CoQ10, precooling, supplementation with precooling, and control. Blood sampling was done pre and post (before and after acute recoding bout) administration of CoQ10 and pre-cooling. There was no significant statistical difference among groups for the indices levels of IL-10, IL-8, IL-6, TNF-α, hs-CRP, catecholamine, cortisol, MPO, XO, and WBC counts at the pre sampling (P > 0.05). While, pre-cooling and control groups show a significant increase indices levels compared to the supplementation and supplementation with precooling groups in the post-sampling (two stages), (P ˂ 0.05). Short-term oral CoQ10 supplementation prevents adverse changes mediators of inflammatory cytokines following heavy swimming trainings and acute recording bout. In addition, pre-cooling strategy individually has no desired effect on the mediators of inflammatory cytokines.

Exercise training, circulating cytokine levels and immune function in cancer survivors: A meta-analysis.

BACKGROUND: Anti-cancer therapies lead to chronic non-resolving inflammation and reduced immune function. One potential therapy is exercise training, but the effectiveness of these interventions to improve immune-related outcomes, the gaps in the literature, and recommendations to progress the field need to be determined. OBJECTIVES: (1) to conduct separate meta-analyses in cancer survivors to determine the effects of exercise training on pro- and anti-inflammatory markers, and immune cell proportions and function; and (2) to perform subgroup analyses to determine whether exercise modality, cancer type, and specific markers help to explain heterogeneity in each meta-analysis. DATA SOURCES: Electronic databases (PubMed/MEDLINE, EMBASE, CENTRAL, and CINAHL) from inception to March 2018. The reference lists of eligible articles and relevant reviews were also checked. STUDY SELECTION: Inclusion criteria were adult cancer survivors from randomized controlled trials performing structured exercise intervention (aerobic, resistance or combined training or Tai Chi/yoga) compared to usual care control group and included pro-inflammatory, anti-inflammatory, and/or immune cell outcomes. APPRAISAL AND SYNTHESIS METHODS: A total of 5349 potentially eligible articles were identified, of which 26 articles (27 trials) met the inclusion criteria. Effect sizes were calculated as standardized mean differences (SMD), where <0.2 was defined as trivial, 0.2-0.3 as small, 0.4-0.8 as moderate, and >0.8 as a large effect. RESULTS: Exercise training decreased pro-inflammatory markers (SMD: -0.2, 95% CI: -0.4, -0.1, p < 0.001). Sub-group analysis for the pro-inflammatory markers indicated that combined aerobic and resistance training had the greatest effect (SMD: -0.3, 95% CI: -0.5, -1.9, p < 0.001), that prostate (SMD: -0.5, 95% CI: -0.8, 0.1, p = 0.004) and breast cancer populations were most responsive (SMD: -0.2, 95% CI: -0.3, -0.1, p = 0.001), and that C-reactive protein (SMD: -0.5, 95% CI: -0.9, -0.06, p = 0.025) and tumor necrosis factor (SMD: -0.3, 95% CI: -0.5, -0.06, p = 0.004) were the most sensitive to change. Exercise training tended to decrease anti-inflammatory markers (p = 0.072) but had no effect on natural killer or natural killer T cell proportions or cytotoxic activity. CONCLUSIONS: Exercise training reduces pro-inflammatory markers in cancer survivors, with the strongest evidence for combined training and for prostate and breast cancer survivors. Further research is warranted to determine if these changes are clinically relevant or are associated with improvements in symptoms. To strengthen future research, focusing on novel immune populations that include functional parameters and standardized reporting of key immune outcomes is recommended.

The Effect of Iranian Propolis on Glucose Metabolism, Lipid Profile, Insulin Resistance, Renal Function and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Clinical Trial.

Propolis is a natural product with many biological properties including hypoglycemic activity and modulating lipid profile. The present study was designed to evaluate the effect of Iranian propolis extract on glucose metabolism, Lipid profile, Insulin resistance, renal and liver function as well as inflammatory biomarkers in patients with type 2 diabetes mellitus (T2DM). A double-blind, placebo-controlled clinical trial was conducted. The duration of the study lasted 90 days. Patients with T2DM were recruited and randomly divided into an Iranian propolis group (1000 mg/day) (n = 50) and a placebo group (n = 44). There was a significant decrease in the serum levels of glycosylated hemoglobin (HbA1c), 2-hour post prandial (2hpp), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), homeostasis model assessment of ß-cell function (HOMA-ß), High sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α). However, there was a notable elevation in the serum HDL-C in the propolis group compared with the placebo group. In addition, a notable reduction in serum liver transaminase (ALT and AST) and blood urea nitrogen (BUN) concentrations in the propolis group was observed. Iranian propolis has beneficial effects on reducing post prandial blood glucose, serum insulin, insulin resistance, and inflammatory cytokines. It is also a useful treatment for preventing the liver and renal dysfunction, as well as, elevating HDL-C concentrations in patients with T2DM.

Effect of L-carnitine and conjugated linoleic acid supplements on haemoglobin levels and haptoglobin genotype in chronic kidney disease.

OBJECTIVE: To investigate the efficacy of L-carnitine (LC) and conjugated linoleic acid (CLA) supplements on haemoglobin levels and inflammatory markers in chronic kidney disease (CKD) patients with different haptoglobin (HP) genotypes. METHODS: This clinical trial study was conducted at Imam Khomeini Hospital, Ardabil, and Labbafinejad Hospital, Tehran, Iran, from March 2014 to March 2015, and comprised male patients with CKD and anaemia. Anthropometric factors were recorded and demographic data was collected using general questionnaires. LC (1 g/day) and CLA (2.4 g/day) supplements were given to the patients for a month. Blood samples were taken to measure haematological and inflammatory markers at the beginning and end of the study. Haptoglobin genotypes were determined using polymerase chain reaction (PCR). SPSS 21 was used for data analysis. RESULTS: Among the 40 patients in the study, HP2-2 genotype was the most prevalent genotype (62.5%). The level of haemoglobin was significantly increased in the patients at the end of the study (p< 0.05). No significant changes were found in the weight, body mass index and serum levels of Interleukin-6, high-sensitivity C-reactive protein, ferritin, total iron-binding capacity and iron (p>0.05 each). CONCLUSIONS: Regular diet supplementation with LC plus CLA can improve haemoglobin levels in CKD patients with anaemia.

An evaluation of the effect of saffron supplementation on the antibody titer to heat-shock protein (HSP) 70, hsCRP and spirometry test in patients with mild and moderate persistent allergic asthma: A triple-blind, randomized placebo-controlled trial.

BACKGROUND: Asthma is a heterogeneous disease, which usually associated with chronic airway inflammation. The anti-heat shock protein (anti-HSP) 70 is a novel risk factor for asthma. The aim of the present study was to survey the effect of saffron supplementation on anti-HSP70, high-sensitivity C-reactive protein (hs-CRP) and spirometry test in patients with allergic asthma. BASIC PROCEDURES: In this clinical trial, patients (N = 80, 32 women and 48 men, 18-65 years old) with mild and moderate allergic asthma were randomized into two groups: a group of patients who received two capsules of saffron (100 mg/d) and a control group who received two capsules of placebo for 8 weeks. Anti-HSP70, hs-CRP and spirometry test were determined in patients before (week 0) and after (week 8) intervention. SPSS software (version 16.0; Inc, Chicago, IL) was used for data analysis. MAIN FINDINGS: Saffron in comparison with placebo significantly reduced the hs-CRP (p < 0.001) and anti-HSP70 (p < 0.001) concentrations. In spirometry test, forced expiratory volume in first second(FEV1), forced vital capacity (FVC), FEV1/FVC ratio and forced expiratory flow 25-75%.(FEF 25-75) increased significantly in saffron in comparison to placebo group (p < 0.05). PRINCIPAL CONCLUSIONS: Results of the present study suggested that saffron supplementation in patients with allergic asthma decreased significantly anti-HSPs 70 and hs-CRP and also improved some spirometry test factors.

Sodium tanshinone IIA sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis.

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg-1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.

Effects of acupuncture on chronic idiopathic pruritus: an uncontrolled pilot study evaluating inflammatory changes with treatment.

Background Conduct a pilot study addressing the efficacy of acupuncture in the treatment of chronic idiopathic pruritus to aid in the design of a larger clinical trial. Routine laboratory tests to assess systemic inflammation in addition to subjective patient surveys were performed provide documentation of efficacy of treatment. Methods Patients with chronic pruritus who did not respond to standard treatment were recruited to participate. After exclusion of systemic or known reversible causes, each patient received up to 10 treatments which were performed approximately one week apart. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured before and after a series of acupuncture treatments to evaluate levels of inflammation and pre- and post-treatment surveys were conducted to evaluate levels of perceived itch. Results Only one of the ten patients in this study possessed an elevation of ESR before treatment. This patient's ESR value returned to normal range after treatment and this participant reported subjective relief of her pruritus. Conclusions Future studies on the efficacy of acupuncture in the treatment of chronic idiopathic pruritus should focus on those patients with measurable levels of inflammation at the initiation of the study or utilize alternative and more comprehensive values to monitor disease response.

Korean Red Ginseng Protects Against Mitochondrial Damage and Intracellular Inflammation in an Animal Model of Type 2 Diabetes Mellitus.

Korean red ginseng (KRG), a heat-processed Korean ginseng (Panax ginseng C.A. Meyer), has been used as a traditional medicine for its beneficial effects on hyperglycemia. This study aimed to investigate whether the antidiabetic action of KRG in an animal model of type 2 diabetes mellitus (DM) is partly mediated by prevention of mitochondrial dysfunction and intracellular inflammation. Four-week-old C57BL/KsJ db/db mice (a genetic animal model of obese type 2 DM) and C57BL/KsJ db/+ mice were divided into three groups: db/+ mice (normoglycemic control group, n = 8), db/db mice (untreated DM group, n = 8), and db/db mice with KRG administration (KRG-treated DM group, n = 8). After 12 weeks, metabolic parameters of fasting blood glucose concentrations, hemoglobin A1c (HbA1c) level, insulin level, lipid profile, and leukocyte count were determined using high-performance liquid chromatography. Mitochondrial DNA (mtDNA) copy number and inflammatory marker (interleukin-6, cyclooxygenase-2, and C-reactive protein) expression levels were measured in skeletal muscle tissue using quantitative real-time PCR analysis. After 12 weeks of KRG treatment at 100 mg/kg, the fasting glucose, HbA1c, insulin, and low-density lipoprotein cholesterol concentrations were lower, whereas mtDNA copy numbers were higher in the KRG-treated DM group than in the untreated DM group. Compared with the untreated DM group, the messenger RNA expression levels of mitochondrial biogenesis-related transcription factors and inflammatory markers were lower in the KRG-treated DM group. In conclusion, KRG had a beneficial effect on the metabolic profile by preserving mitochondrial function and protecting against intracellular inflammation.

Effect of Circular ANRIL on the Inflammatory Response of Vascular Endothelial Cells in a Rat Model of Coronary Atherosclerosis.

BACKGROUND/AIMS: This study aims to investigate the role of circular antisense non-coding RNA at the INK4 locus (cANRIL) in the inflammatory response of vascular endothelial cells (ECs) in a rat model of coronary atherosclerosis (AS). A rat model of AS was established with rats that were injected with a large dose of vitamin D3 and fed a high-fat diet. METHODS: Sixty Wistar rats were randomly assigned into control, model, empty vector, over-expressed cANRIL and low-expressed cANRIL groups (12 rats in each group). Sixteen weeks later, the ultrastructure of their coronary arteries was observed via transmission electron microscopy. Rat serum lipid levels were analyzed using an automatic biochemical analyzer, and their atherogenic index (AI) values were calculated. Hematoxylin and eosin staining was used to observe the endothelial morphology of rats. Additionally, rat EC apoptosis was tested via a TUNEL assay. Enzyme-linked immunosorbent assays (ELISAs) were applied to measure serum levels of interleukin-1 (IL-1), IL-6, matrix metalloproteinase-9 (MMP-9) and C-reactive protein (CRP). The cANRIL, Bax, bcl-2 and caspase-3 mRNA expression levels were measured with a quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Bax, bcl-2 and caspase-3 were detected using immunohistochemistry. RESULTS: In the control group, ECs were closely arranged with normal structures, and there was no proliferation. In the model, empty vector and over-expressed cANRIL groups, some cells were not present, and atherosclerotic plaques and thrombi appeared. However, in the under-expressed cANRIL group, the cells had a normal structure. Compared with the model and empty vector groups, the levels of total cholesterol (CHOL), triglycerides (TGs), low density lipoprotein (LDL), IL-1, IL-6, MMP-9, CRP, cANRIL, Bax, and caspase-3, AI values, and rates of EC apoptosis decreased in the low-expressed cANRIL group, while HDL (high density lipoprotein) levels and mRNA and protein expression levels of bcl-2 were increased. The changes in expression levels in the over-expressed cANRIL group were the opposite of those in the low-expressed cANRIL group. CONCLUSIONS: Our study provides evidence that reduced cANRIL expression could prevent coronary AS by reducing vascular EC apoptosis and inflammatory factor expression.

Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography.

Importance: Inflammation is critical in the development of atherosclerosis. Psoriasis is a chronic inflammatory skin disease that is associated with increased vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography in vivo and future cardiovascular events. It provides a human model to understand the effect of treating inflammation in a target organ (eg, the skin) on vascular diseases. Objective: To investigate the association between change in skin disease severity and change in vascular inflammation at 1 year and to characterize the impact of 1 year of anti-tumor necrosis factor therapy on vascular inflammation. Design, Setting, and Participants: In this prospective cohort study, 220 participants from outpatient practices were recruited at the US National Institutes of Health. A total of 115 consecutively recruited patients with psoriasis were followed up at 1 year. The study was conducted from January 1, 2013, through October 31, 2016, with data analyzed in November 2016. Exposure: Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score. Main Outcomes and Measures: Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography. Results: Among the 115 patients, the mean (SD) age at 1-year follow-up was 50.8 (12.8) years and 68 were men (59%). The cohort had a low cardiovascular risk by Framingham risk score and mild-to-moderate psoriasis, with a median PASI score of 5.2 (interquartile range, 3.0-8.9). At follow-up, the total cohort had a median improvement in PASI score of 33%, with use of topical therapy (60%), biological therapy (66%, mostly anti-tumor necrosis factor) and phototherapy (15%) (P < .001). Moreover, improvement in PASI score was associated with improvement in target-to-background ratio of 6%, mainly driven by those with higher responses in PASI score (P < .001). This association persisted beyond traditional risk factors (ß = 0.19; 95% CI, 0.012-0.375; P = .03) and was the strongest in those initiated with anti-tumor necrosis factor therapy (ß = 0.79; 95% CI, 0.269-1.311; P = .03). Conclusions and Relevance: Improvement in psoriasis skin disease severity was associated with improvement in aortic vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography, with greater improvement in aortic vascular inflammation observed in those who had higher than 75% reduction in skin disease severity. These findings suggest that controlling remote target organ inflammation (eg, in the skin) may improve vascular diseases; however, randomized clinical trials are needed to confirm these findings.

Altered glycan accessibility on native immunoglobulin G complexes in early rheumatoid arthritis and its changes during therapy.

The goal of this study was to investigate the glycosylation profile of native immunoglobulin (Ig)G present in serum immune complexes in patients with rheumatoid arthritis (RA). To accomplish this, lectin binding assays, detecting the accessibility of glycans present on IgG-containing immune complexes by biotinylated lectins, were employed. Lectins capturing fucosyl residues (AAL), fucosylated tri-mannose N-glycan core sites (LCA), terminal sialic acid residues (SNA) and O-glycosidically linked galactose/N-acetylgalactosamine (GalNac-L) were used. Patients with recent-onset RA at baseline and after 3-year follow-up were investigated. We found that native IgG was complexed significantly more often with IgM, C1q, C3c and C-reactive protein (CRP) in RA patients, suggesting alterations of the native structure of IgG. The total accessibility of fucose residues on captured immune complexes to the respective lectin was significantly higher in patients with RA. Moreover, fucose accessibility on IgG-containing immune complexes correlated positively with the levels of antibodies to cyclic citrullinated peptides (anti-CCP). We also observed a significantly higher accessibility to sialic acid residues and galactose/GalNAc glyco-epitopes in native complexed IgG of patients with RA at baseline. While sialic acid accessibility increased during treatment, the accessibility of galactose/GalNAc decreased. Hence, successful treatment of RA was associated with an increase in the SNA/GalNAc-L ratio. Interestingly, the SNA/GalNAc-L ratio in particular rises after glucocorticoid treatment. In summary, this study shows the exposure of glycans in native complexed IgG of patients with early RA, revealing particular glycosylation patterns and its changes following pharmaceutical treatment.

Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.

The aims of this meta-analysis were to evaluate the effects of coenzyme Q10 (CoQ10) supplementation on inflammatory mediators including C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by analyzing published randomized controlled trials (RCTs). A systematic search in PubMed, Cochrane Library and Clinicaltrials.gov was performed to identify eligible RCTs. Data synthesis was performed using a random- or a fixed-effects model depending on the results of heterogeneity tests, and pooled data were displayed as weighed mean difference (WMD) and 95% confidence interval (CI). Seventeen RCTs were selected for the meta-analysis. CoQ10 supplementation significantly reduced the levels of circulating CRP (WMD: -0.35mg/L, 95% CI: -0.64 to -0.05, P=0.022), IL-6 (WMD: -1.61pg/mL, 95% CI: -2.64 to -0.58, P=0.002) and TNF-α (WMD: -0.49pg/mL, 95% CI: -0.93 to -0.06, P=0.027). The results of meta-regression showed that the changes of CRP were independent of baseline CRP, treatment duration, dosage, and patients characteristics. In the meta-regression analyses, a higher baseline IL-6 level was significantly associated with greater effects of CoQ10 on IL-6 levels (P for interaction=0.006). In conclusion, this meta-analysis of RCTs suggests significant lowering effects of CoQ10 on CRP, IL-6 and TNF-α. However, results should be interpreted with caution because of the evidence of heterogeneity and limited number of studies.

Effect of a Single Dose of Vitamin D3 on Postprandial Arterial Stiffness and Inflammation in Vitamin D-Deficient Women.

CONTEXT: Cholecalciferol (vitamin D3) improves vascular function and inflammation, potentially providing an explanation for the proposed cardiovascular protection of vitamin D. OBJECTIVE: We investigated whether cholecalciferol supplementation reduces postprandial arterial dysfunction and inflammation. DESIGN: Randomized, 1:1, double-blind trial. SETTING: Diabetes and Vascular Center, Franciscus Gasthuis, Rotterdam, The Netherlands. PATIENTS: Twenty-four healthy, premenopausal, overweight or obese, vitamin D-deficient women. INTERVENTIONS: A single high (300,000 IU) or low dose (75,000 IU) of cholecalciferol. MAIN OUTCOME MEASURES: The effect of low- and high-dose cholecalciferol on postprandial leukocyte activation markers, pulse wave velocity (PWV), and augmentation index (AIx) during an oral fat loading test, expressed as area under the curve (AUC). RESULTS: High- and low-dose supplementation increased vitamin D by 163% ± 134% (P < 0.001) and 66% ± 59% (P < 0.001), respectively. Monocyte CD11b-AUC slightly increased after low but not high dose (6% ± 2%, P = 0.012, and 4% ± 1%, P = 0.339, respectively). There were no significant effects on postprandial PWV or AIx by high- or low-dose vitamin D. Fasting complement component 3 (C3) levels decreased by 5.9% (P = 0.004) in the high-dose group and by 4.0% (P = 0.018) in the low-dose group. CONCLUSION: A single dose of vitamin D does not seem to reduce arterial stiffness and leukocyte activation in overweight, vitamin D-deficient women. Vitamin D may decrease fasting C3. Possibly, higher vitamin D concentrations may be needed to decrease inflammation and improve vascular function in overweight or obese vitamin D-deficient women.

Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy.

BACKGROUND: Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. METHODS: 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion. RESULTS: At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-ß than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-ß levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-ß changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT. LIMITATIONS: As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. CONCLUSIONS: Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-ß, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation.

Effect of Vitamin D3 Supplementation on Inflammatory Markers and Glycemic Measures among Overweight or Obese Adults: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Obesity induced low-grade chronic inflammation disrupts proper immune and metabolic function. Vitamin D deficiency increases inflammation, which is associated with cardiometabolic risk. This systematic review examines the association between oral vitamin D (VD) supplementation and circulating inflammatory biomarkers and glycemic outcomes from randomized controlled trials (RCTs) of overweight and/or obese adults. METHODS: MEDLINE OVID, EMBASE and the Cochrane Central Register of Controlled Trials were searched according to a predefined protocol. Eligible RCTs included adults randomized to receive either oral VD or placebo. Two reviewers independently assessed RCTs for inclusion. Bias was assessed using the Cochrane Collaboration risk of bias tool. Mean differences were calculated comparing end-of-study sample means between the independent VD and placebo groups. RESULTS: Eleven unique RCTs met inclusion criteria from a total of 3,383 identified citations, including 79 screened articles and 14 full text data extractions. Inflammatory and glycemic measures were reported in 7 and 10 RCTs, respectively. Most trial findings were non-significant with considerable heterogeneity in design, participants and outcomes. All but one trial was rated as either high or unclear risk of bias. Two RCTs reported significant changes in inflammatory biomarkers; however, the mean difference between groups was not statistically significant: C-reactive protein 0.19 mg/L (p = 0.88); Tumor Necrosis Factor -0.54 pg/ml (p = 0.20). Two other trials found significant mean differences in fasting plasma glucose -0.32 mmol/L (p = 0.03), Hemoglobin A1c -0.13% (p = 0.04), and Homeostatic Model Assessment -0.86 (p = 0.02) following VD supplementation. CONCLUSIONS: Overall, there is no clear established benefit of VD supplementation on inflammatory biomarkers among overweight/obese adults. Baseline serum VD possibly influences the effect of VD repletion on inflammatory markers. Risk of bias was present in most studies, thus supporting the need for higher quality studies in this area to more conclusively understand the role VD supplementation has on inflammatory pathways.