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1.
Modulation of Cardiometabolic Disease Markers by Type I Interferon Inhibition in Systemic Lupus Erythematosus.
Casey, KA, Smith, MA, Sinibaldi, D, Seto, NL, Playford, MP, Wang, X, Carlucci, PM, Wang, L, Illei, G, Yu, B, et al
Arthritis & rheumatology (Hoboken, N.J.). 2021;(3):459-471
Abstract
OBJECTIVE Neutrophil dysregulation and the type I interferon (IFN) axis have been proposed to contribute to premature cardiovascular disease, a leading cause of mortality in patients with systemic lupus erythematosus (SLE). In the present study, we evaluated the ability of anifrolumab, a type I IFN receptor-blocking antibody, to reduce neutrophil extracellular trap (NET) formation and modulate cardiometabolic disease markers in comparison to placebo. METHODS Study subjects comprised patients with moderate-to-severe SLE who were enrolled in phase IIb of the MUSE trial (A Phase II, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects with Systemic Lupus Erythematosus), with healthy individuals as controls. Blood samples were collected from SLE patients (n = 305) and healthy controls (n = 10-20) before the initiation of treatment (baseline) and from SLE patients after they had been treated with 300 mg of anifrolumab (n = 99) or placebo (n = 102). Baseline IFN gene signature test status was determined, and the IFN gene signature (21-gene panel) was monitored over time. Serum proteins were measured by multiplex immunoassay or ultrasensitive Simoa assay. NET complexes, cholesterol efflux capacity (CEC), and glycoprotein acetylation (GlycA) and other lipid parameters were assessed in plasma. RESULTS Formation of NET complexes and levels of tumor necrosis factor (TNF) and interleukin-10 (IL-10) were correlated with extent of type I IFN pathway activity. NET complexes and IL-10 levels were up-regulated in SLE patients compared to healthy controls (P < 0.008). The cardiometabolic disease markers CEC and GlycA were also found to be dysregulated in patients with SLE (P < 0.001 versus healthy controls). Type I IFN receptor inhibition with anifrolumab significantly reduced NET complexes and GlycA and improved CEC compared to baseline (P < 0.05) whereas no improvements were seen with placebo. Levels of TNF and IL-10 were reduced with anifrolumab compared to placebo (P < 0.05). CONCLUSION These data support a key role for type I IFNs in modulating factors contributing to SLE vasculopathy and suggest that inhibition of this pathway could decrease cardiovascular risk in individuals with SLE.
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2.
The acute effect of incorporating lettuce or watercress into a moderately high-fat meal on postprandial lipid, glycemic response, and plasma inflammatory cytokines in healthy young men: a randomized crossover trial.
Shokraei, S, Khandouzi, N, Sina, Z, Nasrollahzadeh, J
Lipids in health and disease. 2021;(1):66
Abstract
BACKGROUND Postprandial responses to food mostly depend on the composition of the meal and the consumption of vegetables may modulate this postprandial state. In this study, the effects of lettuce or watercress consumption with a moderately high-fat meal (40% kcal from fat) on postprandial lipemia, glycemia, and inflammatory cytokines were determined in healthy men. METHODS This randomized, 3-arm, crossover study was conducted in sixteen healthy young men with a mean ± SEM age and body mass index (in kg/m2) of 22.8 ± 0.5 years old and 23.7 ± 1.16, respectively. Lettuce and watercress were added to the test meal in portions of 100 g and cellulose was added to the control meal. Thereafter, blood samples were collected by passing 0, 1, 2, 3, and 4 h for analysis. The postprandial response was measured in plasma glucose, triglycerides (TG), total cholesterol, high-density-lipoproteins cholesterol (HDL-C), and low-density-lipoproteins cholesterol (LDL-C), as the area under the postprandial curve (AUC). Moreover, plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined once before and once 4 h after the meal's consumption. RESULTS The 0-4-h AUCs for glucose (385.7, 361.9, and 382.3 mg/dL for the control, lettuce, and watercress meals, respectively) were calculated to be lower when meal was consumed with lettuce compared to the control (P < 0.05) and watercress (P < 0.01) meals. The maximum values of insulin were obtained as 43.8 ± 18.8, 33.5 ± 19.5, and 42.8 ± 17.7 μIU/mL for the control, lettuce, and watercress meals, respectively. As well, the lettuce-containing meal more reduced the AUC for insulin compared with the control (P < 0.05), but not watercress. Notably, plasma TG, total cholesterol, HDL-C, and LDL-C had no significant differences among the meals. Moreover, the levels of plasma IL-6 and TNF-α did not differ among the meals. CONCLUSION In this study on healthy men, the addition of lettuce to a moderately high-fat meal delayed the postprandial glycemic response. However, the effect of the consumption of these vegetables on postprandial responses in subjects with cardiometabolic risk factors remains to be elucidated yet. This clinical trial was registered at the Iran Clinical Trials Registration Office (IRCT) on March 3, 2018, with an ID of IRCT20160702028742N4 ( https://www.irct.ir/user/trial/23233/view ).
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3.
Synergism Effects of Ursolic Acid Supplementation on the Levels of Irisin, C-reactive Protein, IL-6, and TNF-α During High-intensity Resistance Training in Low Activity Men.
Asghari, E, Rashidlamir, A, Hosseini, SRA, Moazzami, M, Samarghandian, S, Farkhondeh, T
Cardiovascular & hematological disorders drug targets. 2020;(2):138-144
Abstract
BACKGROUND Ursolic Acid (UA) is a pentacyclic triterpenoid carboxylic acid which is extracted from plants. UA may enhance the effect of Resistance Training (RT) in human. OBJECTIVE Current research was designed to show the effect of High-Intensity Resistance Training (HIRT) in the presence or absence of UA on the serum levels of irisin, CRP, IL-6 and TNF-α in the low activity men. METHODS The study included twenty-two healthy male HIRT with placebo, supplementation, and HIRT in the presence of UA supplementation. The two groups received eight-week intervention including 2 sets of 8 exercises, with 8~10 repetitions at 70~75% of 1 repetition maximum and a 2 min rest interval between sets, performed 3 times/week. Placebo or UA orally was evaluated as 1 capsule 3 times/day during 8 weeks. The subsequent factors were measured post- and preintervention: C-Reactive Protein (CRP), Irisin, Tumor Necrotic Factor (TNF-α) and Interleukin-6 (IL-6). RESULTS UA supplementation significantly increased the plasma levels of irisin in the HIRT+UA group versus the HIRT+P group (p<0.05). UA treatment also dramatically decreased the plasma levels of CRP, IL-6, and TNF-α in the HIRT+UA group versus the HIRT+P group (p<0.05). CONCLUSION The current data showed that UA-induced an increase in serum irisin and reduction of CRP, IL-6, and TNF-α may have beneficial effects as a chemical for increasing of the effects of HIRT in low activity men.
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4.
Perinatal inflammation and childhood adiposity - a gender effect?
Donnelly, JM, Lindsay, K, Walsh, JM, Horan, MK, O'Shea, D, Molloy, EJ, McAuliffe, FM
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;(7):1203-1210
Abstract
Background: To determine the association of maternal and fetal inflammatory factors with gender-specific infant adiposity, independent of leptin.Methods: Analysis of anthropometry from 265 mother-infant pairs at birth and 280 pairs at 6 months from the randomised control trial of low glycaemic index diet in pregnancy (ROLO) study (Randomised control trial of low glycaemic index diet) and their association with Maternal TNF-alpha, interleukin 6 and leptin as measured in early and late pregnancy and fetal levels in cord blood.Results: No associations were noted in the male cohort. On multiple regression amongst the female neonatal cohort late pregnancy IL-6 was inversely associated with sum of skinfolds (p ≤ .001); at 6 months infant sum of skinfolds were positively associated with early pregnancy IL-6 (p = .046) and central adiposity positively associated with early pregnancy TNF alpha (p = .018) independent of leptin.Conclusion: Although maternal inflammatory cytokines were not associated with neonatal adiposity independent of leptin (as this association is known), both IL-6 and TNF-α were associated with female infant anthropometry at 6 months of age independent of leptin. These results suggest inflammatory cytokines may exert an in-utero influence on later infant adiposity with a tendency to influence female adiposity more than male. Further research is required to ascertain whether these cytokines may be used as reliable early predictors of infant adiposity.
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5.
Effect of Vitamin D Supplementation on Inflammatory Markers in Non-Obese Lebanese Patients with Type 2 Diabetes: A Randomized Controlled Trial.
El Hajj, C, Walrand, S, Helou, M, Yammine, K
Nutrients. 2020;(7)
Abstract
BACKGROUND A low serum 25-hydroxyvitamin D (25(OH) D) concentration has been associated with a higher risk of type 2 diabetes mellitus (T2DM), especially in older people. Our aim in this randomized controlled trial was to evaluate the effect of vitamin D treatment on inflammatory markers in non-obese Lebanese patients with T2DM, living in Beirut, Lebanon. METHODS Non-Obese patients with T2DM (n = 88), deficient/insufficient in vitamin D, were randomly assigned into one of two groups-a treatment group receiving 30,000 IU cholecalciferol/week for a period of six months, and a placebo group. Serum concentrations of TNF-α, high-sensitivity C-reactive protein (hs-CRP), and Interleukin-6 (IL-6) were the primary outcomes. A homeostatic model of insulin resistance (HOMA-IR) was assessed, in addition to serum concentrations of fasting blood glucose (FBG), HbA1C, (25(OH) D), and PTH. RESULTS The vitamin D group showed higher blood levels of (25(OH) D) (p < 0.0001), and a significant reduction in hs-CRP and TNF-α concentrations (p < 0.0001) compared to placebo. The decrease perceived in IL-6 concentrations was not significant (p = 0.1). No significant changes were seen in FBG (p = 0.9) and HbA1c levels (p = 0.85). CONCLUSION Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients with T2DM. Additional studies with a larger sample and a longer period are advised in this regard. This trial was registered at ClinicalTrial.gov; Identifier number: NCT03782805.
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6.
Immune activation of Bio-Germanium in a randomized, double-blind, placebo-controlled clinical trial with 130 human subjects: Therapeutic opportunities from new insights.
Cho, JM, Chae, J, Jeong, SR, Moon, MJ, Shin, DY, Lee, JH
PloS one. 2020;(10):e0240358
Abstract
[NCT03677921]; www.clinicaltrials.gov [KCT0002726]; https://cris.nih.go.kr.
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7.
Effects of macular xanthophyll supplementation on brain-derived neurotrophic factor, pro-inflammatory cytokines, and cognitive performance.
Stringham, NT, Holmes, PV, Stringham, JM
Physiology & behavior. 2019;:112650
Abstract
PURPOSE Oxidative and inflammatory processes play a major role in stress-induced neural atrophy. There is a wide body of literature linking oxidative and inflammatory stress with reductions in neurotrophic factors, stress resilience, and cognitive function. Based on their antioxidant and anti-inflammatory capacity, we investigated the effect of the dietary carotenoids lutein and zeaxanthin, along with the zeaxanthin isomer meso-zeaxanthin (collectively the "macular xanthophylls" [MXans]) on systemic brain-derived neurotrophic factor (BDNF) and anti-oxidant capacity (AOC), and the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. To investigate higher-order effects, we assessed cognitive performance. METHODS 59 young (18-25 yrs.), healthy subjects participated in a 6-month, double-blind, placebo-controlled trial to evaluate the effects of MXan supplementation on the aforementioned serum parameters and cognitive performance. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg/day total MXans; all measures were taken at baseline and 6 months. Blood was obtained via fasting blood draw, and MXan concentration in the retina (termed macular pigment optical density [MPOD]) was measured via customized heterochromatic flicker photometry. Serum BDNF and cytokines were assessed via ELISA. Serum antioxidant capacity (AOC) and serum MXan concentrations were quantified via colorimetric microplate assay, and high-performance liquid chromatography, respectively. Cognitive performance was measured via a computer-based assessment tool (CNS Vital Signs). RESULTS BDNF, MPOD, serum MXans, and AOC all increased significantly versus placebo in both treatment groups over the 6-month study period (p < .05 for all). IL-1β decreased significantly versus placebo in both treatment groups (p = .0036 and p = .006, respectively). For cognitive measures, scores for composite memory, verbal memory, sustained attention, psychomotor speed, and processing speed all improved significantly in treatment groups (p < .05 for all) and remained unchanged in the placebo group. Several measures were found to be significantly associated in terms of relational changes over the course of the study. Notably, change in BDNF was related to change in IL-1β (r = -0.47; p < .001) and MPOD (r = 0.44; p = .0086). Additionally, changes in serum MXans were strongly related to AOC (r = 0.79 & 0.61 for lutein and zeaxanthin isomers respectively; p < .001). For cognitive scores, change in BDNF was correlated to change in composite memory (r = 0.32; p = .014) and verbal memory (r = 0.35; p = .007), whereas change in MPOD was correlated with change in both psychomotor speed (r = 0.38; p = .003), and processing speed (r = 0.35; p = .007). Change in serum lutein was found to be significantly correlated to change in verbal memory (r = 0.41; p < .001), composite memory (r = 0.31; p = .009), and sustained attention (r = 0.28; p = .036). Change in serum zeaxanthin isomers was significantly correlated with change in verbal memory (r = 0.33; p = .017). Lastly, change in AOC was significantly associated with verbal memory (r = 0.34; p = .021), composite memory (r = 0.29; p = .03), and sustained attention (r = 0.35; p = .016). No significant relational changes in any cognitive parameter were found for the placebo group. CONCLUSIONS Six months of daily supplementation with at least 13 mg of MXans significantly reduces serum IL-1β, significantly increases serum MXans, BDNF, MPOD, and AOC, and improves several parameters of cognitive performance. Findings suggest that increased systemic antioxidant/anti-inflammatory capacity (and not necessarily deposition of the carotenoids in neural tissues), may explain many of the effects determined in this study. The significant relationship between change in BDNF and IL-1β over the course of the study suggests that regular consumption of MXans interrupts the inflammatory cascade that can lead to reduction of BDNF. Changes in MPOD and BDNF appear to account for enhancement in cognitive parameters that involve speed of processing and complex processing, respectively. ISRCTN Clinical Trial Registration: ISRCTN16156382.
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8.
Even Short-Term Telmisartan Treatment Ameliorated Insulin Resistance But Had No Influence on Serum Adiponectin and Tumor Necrosis Factor-Alpha Levels in Hypertensive Patients with Metabolic Syndrome.
Kiyici, S, Guclu, M, Budak, F, Sigirli, D, Tuncel, E
Metabolic syndrome and related disorders. 2019;(3):167-172
Abstract
BACKGROUND We investigated the effect of short-term telmisartan usage in addition to lifestyle changes such as diet and exercise on insulin resistance, lipid metabolism, and serum adiponectin and tumor necrosis factor-alpha (TNF-α) levels in hypertensive patients with metabolic syndrome (MetS). METHODS A total of 36 hypertensive patients with MetS were randomized to telmisartan and control groups in an open-labeled prospective study. RESULTS There were significant decreases in anthropometric variables of patients according to baseline measurements in both groups at the end of the study. Serum insulin level and insulin resistance assessed by homeostasis model assessment-insulin resistance were decreased significantly in the telmisartan group (P = 0.040 and P = 0.034, respectively) compared with the controls, while there was no statistically significant change in the lipid profiles of the two groups. Serum adiponectin level was increased by 19.1% ± 41.7% in the telmisartan group, but intergroup analysis revealed no significant change. There was also no significant change in serum TNF-α level in either group. CONCLUSION It has been observed that even short-term telmisartan treatment had favorable effects on insulin resistance and glucose metabolism compared with lifestyle changes alone. The fundamental effect of telmisartan treatment on insulin resistance renders it a good therapeutic option for hypertensive patients with MetS.
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9.
Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids.
Primec, M, Klemenak, M, Di Gioia, D, Aloisio, I, Bozzi Cionci, N, Quagliariello, A, Gorenjak, M, Mičetić-Turk, D, Langerholc, T
Clinical nutrition (Edinburgh, Scotland). 2019;(3):1373-1381
Abstract
BACKGROUND & AIMS Celiac disease (CD) is an immune-mediated systemic disease, caused by ingestion of gluten in genetically predisposed individuals. Gut microbiota dysbiosis might play a significant role in pathogenesis of chronic enteropathies and its modulation can be used as an intervention strategy in CD as well. In this study, we aimed to identify correlations between fecal microbiota, serum tumor necrosis factor alpha (TNF-α) and fecal short-chain fatty acids (SCFAs) in healthy children and children with CD after administration of probiotic Bifidobacterium breve BR03 and B632. METHODS A double-blind placebo-controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC). CD children were randomly allocated into two groups, of which 20 belonged to the placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a probiotic formulation containing a mixture of 2 strains, B. breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for statistical analysis, blood and fecal samples from CD children (on enrolment - T0 and after 3 months, at the end of intervention with probiotic/placebo - T1) and HC children were used. The HC group was sampled only once (T0). RESULTS Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea may be involved in the disease, indicated by a strong correlation to TNF-α. Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The effect of probiotic administration has disclosed a negative correlation between Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and some SCFAs, turning them into an important target in microbiome restoration process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory process in healthy human gut. CONCLUSIONS Our results highlight new phyla, which may have an important relation to disease-related parameters, CD itself and health.
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10.
Resistance training reduces metabolic syndrome and inflammatory markers in older women: A randomized controlled trial.
Tomeleri, CM, Souza, MF, Burini, RC, Cavaglieri, CR, Ribeiro, AS, Antunes, M, Nunes, JP, Venturini, D, Barbosa, DS, Sardinha, LB, et al
Journal of diabetes. 2018;(4):328-337
Abstract
BACKGROUND This study analyzed the effects of a 12-week resistance training (RT) program without dietary interventions on metabolic syndrome (MetS) components and inflammatory biomarkers in older women. METHODS Fifty-three older women (mean [±SD] age 70.4 ± 5.7 years; mean body mass index 26.7 ± 4.0 kg/m2 ) were randomly assigned to a training group (TG; n = 26) that performed 12 weeks of an RT program or a control group (CG; n = 27) that did not perform any type of physical exercise over the same period. Body composition (dual energy X-ray absorptiometry), muscular strength (one-repetition maximum tests), blood pressure (BP), and blood sample measurements were performed before and after intervention. RESULTS After the 12-week period, there were significantly reductions (P < 0.05) in glucose levels (-20.4% vs -0.3%), waist circumference (-1.5% vs +2.0%), and systolic BP (-6.2% vs +0.9%), and complete normalization of MetS prevalence (18% at baseline vs. 0% after 12-weeks RT) in the TG. Moreover, C-reactive protein and tumor necrosis factor-α concentrations decreased in the TG (-28.6% and -21.6%, respectively), but increased in the CG (+34.5% and +13.3%, respectively). In addition there were positive improvements in the MetS Z-score in the TG but not CG (-21.6% vs +13.3%, respectively). CONCLUSION The results suggest that a 12-week RT program seems to effectively reduce MetS components and inflammatory biomarkers in older women, regardless of dietary intervention. The RT-induced adaptations in body composition and inflammatory biomarkers appear to be related to healthy adaptations in risk factors for MetS.