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Effect of Mori ramulus on the postprandial blood glucose levels and inflammatory responses of healthy subjects subjected to an oral high-fat/sucrose challenge: A double-blind, randomized, crossover clinical trial.
Park, SY, Kwon, O, Kim, JY
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112552
Abstract
Blood glucose is inadequately controlled in diabetes mellitus, causing various inflammation-related complications. This study aimed to investigate responses to an oral sucrose/lipid challenge in the context of glucose metabolism after consumption of Mori ramulus (MR) extract. In this study on healthy subjects, the optimal dose and safety of MR were confirmed in a preliminary pilot trial (n = 24), meanwhile, blood glucose, insulin, and inflammatory marker levels were detected via an oral sucrose/lipid tolerance test in the main trial (n = 36). In the main study, the blood glucose response was significantly decreased after 240 min in the MR group. Compared to the placebo group, the treatment group exhibited plasma insulin levels that were significantly increased at 120 min and decreased at 240 min. In conclusion, a single MR extract dose protects against inflammation induced by high-fat/sugar to maintain normal insulin secretion and thus helps to maintain postprandial blood glucose levels via an inflammatory mechanism.
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The effect of atorvastatin on inflammatory markers in sulfur mustard gas induced bronchitis: a randomized double-blinded, placebo-control clinical trial.
Momeni, B, Nazer, S, Masoompour, SM, Geramizadeh, B, Sajadi, SV
BMC pulmonary medicine. 2021;(1):112
Abstract
BACKGROUND This study was performed to evaluate the anti-inflammatory effect of atorvastatin in patients with chronic bronchitis, exposed to sulfur mustard gas. METHODS In this randomized double-blinded clinical trial we recruited patients with chronic bronchitis after exposure to sulfur mustard gas. Ninety men 45-75 years old diagnosed with chronic bronchitis after exposure to mustard gas during the Iran-Iraq war, were randomly assigned to receive either atorvastatin (40 mg) or placebo once a day for 3 months. The interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), procalcitonin, highly sensitive CRP and COPD assessment test (CAT) score was compared at baseline and after 12 weeks. RESULTS After consuming atorvastatin for 12 weeks, IL-6 level (mean difference [95%CI]; 0.2 [- 0.05, 0.5]), TNF-α (mean difference [95%CI]; - 0.07 [- 0.2, 0.07]), high sensitive CRP (mean difference [95%CI] - 0.1 [- 1.2, 0.9]), and procalcitonin (mean difference [95%CI]; 0.003 [- 0.02, 0.03]) did not change significantly. However, in the placebo group, only IL-6 (mean difference [95%CI]; 0.6 [0.2, 1.05]) decreased significantly after 12 weeks, but levels of high sensitive CRP (mean difference [95%CI]; - 0.3 [- 1.4, 0.8]) TNF-α (mean difference [95%CI]; - 0.2 [- 0.34, - 0.06]) and procalcitonin (mean difference [95%CI]; 0.02 [- 0.001, 0.04]) did not change significantly. After 12 weeks, the mean differences in TNF- α, IL-6 level, high sensitive CRP, procalcitonin, and CAT score did not significantly differ between the two groups. CONCLUSIONS The administration of 40 mg atorvastatin for 3 months did not significantly change the inflammatory markers or the quality of life of patients exposed to mustard gas with chronic bronchitis. TRIAL REGISTRATION IRCT, IRCT138904144312N1. Registered 16 August 2014, https://en.irct.ir/trial/4577 .
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Effect of physical activity promotion on adiponectin, leptin and other inflammatory markers in prediabetes: a systematic review and meta-analysis of randomized controlled trials.
Jadhav, RA, Maiya, GA, Hombali, A, Umakanth, S, Shivashankar, KN
Acta diabetologica. 2021;(4):419-429
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Abstract
AIMS: Inflammatory stage in prediabetes is associated with increase in level of adipokines and pro-inflammatory cytokines. Physical activity promotion considered as a first-line therapeutic strategy to treat prediabetes. We have conducted the systematic review and meta-analysis to strengthen the evidence on the impact of physical activity promotion on inflammatory markers in prediabetes. METHODS Studies were identified using electronic search and manual search techniques by choosing keywords for prediabetes, physical activity and inflammatory marker. Randomized controlled trials on individuals diagnosed with prediabetes and provided intervention in the form of physical activity were included in this review. Adiponectin, leptin, C-reactive protein, interleukin-6 and tumour necrosis factor-α were the considered outcome measures. RESULTS Our search retrieved 1,688 citations, 31 full-text articles assessed for eligibility of inclusion. Nine studies satisfied the pre-specified criteria for inclusion. Meta-analysis found that physical activity with or without dietary or lifestyle modification reduces level of leptin (MD-2.11 ng/mL, 95% CI -3.81 - -0.42) and interleukin-6 (MD -0.15 pg/mL, 95% CI -0.25--0.04). It has no effect on level of adiponectin (MD 0.26 µg/mL, 95% CI -0.42- 0.93), C-reactive protein (MD -0.05 mg/L, 95% CI -0.33-0.23) and tumour necrosis factor-α (MD 0.67 pg/mL, 95% CI -2.56-3.89). CONCLUSIONS This review suggests that physical activity promotion with dietary and lifestyle modification may reduce the level of leptin and interleukin-6 but are uncertain if there is any effect on levels of adiponectin, C-reactive protein and tumour necrosis factor-α in the individuals with prediabetes.
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Effect of atorvastatin versus rosuvastatin on inflammatory biomarkers and LV function in type 2 diabetic patients with dyslipidemia.
Werida, R, Khairat, I, Khedr, NF
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:111179
Abstract
BACKGROUND Statins are potential drugs for decreasing risk of atherosclerotic cardiovascular complications in type 2 diabetic (T2D) patients. PURPOSE To examine the efficacy of both rosuvastatin (ROSUVA) and atorvastatin (ATORVA) on LV function and markers of inflammation in T2D patients with dyslipidemia. METHODS One hundred-sixty T2D patients were assigned to receive either atorvastatin (ATORVA group, n = 80, 40 mg) or rosuvastatin (ROSUVA group, n = 80, 10 mg), daily for 6 months. Blood was collected for biochemical analysis. The prevalence of left ventricular abnormalities was determined by echocardiography and two-dimensional Speckle-Strain to assess Global Longitudinal Strain (GLS). RESULTS ROSUVA vs. ATORVA resulted in significant (p < 0.001) reduction in HbA1c % (9.13 vs 2.35%), LDL-C (22.23% vs. 14.75%), triglycerides (13.56 % vs. 8.21 %), total cholesterol (16.10 % vs. 10.81 %), atherogenic index (18.08. % vs. 10.97%), hs-CRP (23.51 % vs.18.96%), sortilin (33.33 % % vs. 15.08 %), and leptin (31.81 % vs. 23.17 %) but increased adiponectin (97.99 % vs.76.47.1 %) and HDL-C (76.47 % vs. 0.21 %) compared with baseline, respectively. Negative correlations between adiponectin and each of hs-CRP, HbA1c%, total cholesterol, LDL-C, atherogenic index and leptin were found. Also, left ventricular functions were correlated with adiponectin, lipids, HbA1c% and hs-CRP. The areas under receiver operating characteristic curve (AUC) showed that hs-CRP, leptin, sortlin, leptin, and adiponectin were good predictors for cardiovascular events. CONCLUSION ROSUVA is more efficacious in improving lipid profile, atherogenic index and modulation of inflammatory biomarkers in dyslipidemic T2D patients compared with ATROVA. However, both statins are equivalent as cardioprotective agents in dyslipidemic T2D patients.
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Novel Anti-inflammatory Effects of Canagliflozin Involving Hexokinase II in Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells.
Uthman, L, Kuschma, M, Römer, G, Boomsma, M, Kessler, J, Hermanides, J, Hollmann, MW, Preckel, B, Zuurbier, CJ, Weber, NC
Cardiovascular drugs and therapy. 2021;(6):1083-1094
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Abstract
PURPOSE Vascular inflammation and disturbed metabolism are observed in heart failure and type 2 diabetes mellitus. Glycolytic enzyme hexokinase II (HKII) is upregulated by inflammation. We hypothesized that SGLT2 inhibitors Canagliflozin (Cana), Empagliflozin (Empa) or Dapagliflozin (Dapa) reduces inflammation via HKII in endothelial cells, and that HKII-dependent inflammation is determined by ERK1/2, NF-κB. and/or AMPK activity in lipopolysaccharide (LPS)-stimulated human coronary artery endothelial cells (HCAECs). METHODS HCAECs were pre-incubated with 3 μM or 10 μM Cana, 1 μM, 3 μM or 10 μM Empa or 0.5 μM, 3 μM or 10 μM Dapa (16 h) and subjected to 3 h LPS (1 μg/mL). HKII was silenced via siRNA transfection. Interleukin-6 (IL-6) release was measured by ELISA. Protein levels of HK I and II, ERK1/2, AMPK and NF-κB were detected using infra-red western blot. RESULTS LPS increased IL-6 release and ERK1/2 phosphorylation; Cana prevented these pro-inflammatory responses (IL-6: pg/ml, control 46 ± 2, LPS 280 ± 154 p < 0.01 vs. control, LPS + Cana 96 ± 40, p < 0.05 vs. LPS). Cana reduced HKII expression (HKII/GAPDH, control 0.91 ± 0.16, Cana 0.71 ± 0.13 p < 0.05 vs. control, LPS 1.02 ± 0.25, LPS + Cana 0.82 ± 0.24 p < 0.05 vs. LPS). Empa and Dapa were without effect on IL-6 release and HKII expression in the model used. Knockdown of HKII by 37% resulted caused partial loss of Cana-mediated IL-6 reduction (pg/ml, control 35 ± 5, LPS 188 ± 115 p < 0.05 vs. control, LPS + Cana 124 ± 75) and ERK1/2 activation by LPS. In LPS-stimulated HCAECs, Cana, but not Empa or Dapa, activated AMPK. AMPK activator A769662 reduced IL-6 release. CONCLUSION Cana conveys anti-inflammatory actions in LPS-treated HCAECs through 1) reductions in HKII and ERK1/2 phosphorylation and 2) AMPK activation. These data suggest a novel anti-inflammatory mechanism of Cana through HKII.
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The Effectiveness of Extra Virgin Olive Oil and the Traditional Brazilian Diet in Reducing the Inflammatory Profile of Individuals with Severe Obesity: A Randomized Clinical Trial.
Longhi, R, Santos, ASEAC, López-Yerena, A, Rodrigues, APS, Oliveira, C, Silveira, EA
Nutrients. 2021;(11)
Abstract
We analyzed the effectiveness of two nutritional interventions alone and together, EVOO and the DieTBra, on the inflammatory profile of severely obese individuals. This study was an RCT with 149 individuals aged from 18 to 65 years, with a body mass index ≥ 35 kg/m2, randomized into three intervention groups: (1) 52 mL/day of EVOO (n = 50); (2) DieTBra (n = 49); and (3) DieTBra plus 52 mL/day of EVOO (DieTBra + EVOO, n = 50). The primary outcomes we measured were the-neutrophil-to-lymphocyte ratio (NLR) and the secondary outcomes we measured were the lymphocyte-to-monocyte ratio (LMR); leukocytes; and C reactive protein (CRP). After 12 weeks of intervention, DieTBra + EVOO significantly reduced the total leucocytes (p = 0.037) and LMR (p = 0.008). No statistically significant differences were found for the NLR in neither the intra-group and inter-group analyses, although a slight reduction was found in the DieTBra group (-0.22 ± 1.87). We observed reductions in the total leukocytes and LMR in the three groups, though without statistical difference between groups. In conclusion, nutritional intervention with DietBra + EVOO promotes a significant reduction in inflammatory biomarkers, namely leukocytes and LMR. CRP was reduced in EVOO and DieTBra groups and NLR reduced in the DieTBra group. This study was registered at ClinicalTrials.gov under NCT02463435.
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Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.
Kim, JY, Park, JT, Kim, HW, Chang, TI, Kang, EW, Ahn, C, Oh, KH, Lee, J, Chung, W, Kim, YS, et al
Journal of the American Heart Association. 2021;(16):e021731
Abstract
Background The function of high-density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high-density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high-density lipoprotein cholesterol (HDL-C) level. Presence of inflammation was defined by hs-CRP (high-sensitivity C-reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person-years of follow-up, overall incidence of the primary outcome was 15.8 per 1000 person-years. In multivariable Cox analysis after adjusting for confounders, HDL-C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL-C for risk of extended major adverse cardiovascular events (P=0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL-C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. Conclusions The association between HDL-C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.
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The effects of vitamin D supplementation on inflammatory biomarkers in patients with abnormal glucose homeostasis: A systematic review and meta-analysis of randomized controlled trials.
Dashti, F, Mousavi, SM, Larijani, B, Esmaillzadeh, A
Pharmacological research. 2021;:105727
Abstract
on the level of inflammatory cytokines following vitamin D supplementation among individuals with abnormal glucose homeostasis (AGH) are controversial. Therefore, the present study was conducted on AGH patients to assess the impact of vitamin D on inflammatory cytokines such as CRP, TNF-α and IL-6. A systematic search up to September 2020 was performed through PubMed and Scopus databases. All clinical studies which evaluated the effect of oral vitamin D supplementation on inflammation in patients with AGH were included. The random-effects model was applied to obtain pooled results. For dose-response analysis, we used a fractional polynomial model. Overall, 38 studies, with 46 effect sizes, were included in this study. Combining effect sizes, we found that vitamin D considerably decrease serum concentrations of CRP (weight mean difference (WMD): - 0.67 mg/l; 95%CI: - 0.92, - 0.43; P < 0.001), IL-6 (WMD: -1.93 pg/mL; 95%CI: -2.80, -1.07; P < 0.001) and TNF-α (WMD: -0.81 pg/mL; 95%CI: -1.59, -0.03; P = 0.04). In the dose-response analysis, we failed to find any correlation between dosage of supplements and inflammatory biomarkers concentrations. Summarizing earlier studies, we demonstrated that circulating concentrations of inflammatory cytokines such as CRP, TNF-α, and IL-6 might be decreased following vitamin D supplementation among individuals with AGH.
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The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines, Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners.
Żebrowska, A, Hall, B, Stolecka-Warzecha, A, Stanula, A, Sadowska-Krępa, E
Nutrients. 2021;(2)
Abstract
BACKGROUND The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. METHODS Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. RESULTS A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. CONCLUSIONS The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.
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Effects of Folic Acid Supplementation on Inflammatory Markers: A Grade-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.
Asbaghi, O, Ashtary-Larky, D, Bagheri, R, Moosavian, SP, Nazarian, B, Afrisham, R, Kelishadi, MR, Wong, A, Dutheil, F, Suzuki, K, et al
Nutrients. 2021;(7)
Abstract
It has been theorized that folic acid supplementation improves inflammation. However, its proven effects on inflammatory markers are unclear as clinical studies on this topic have produced inconsistent results. To bridge this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of folic acid supplementation on serum concentrations of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Methods: To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, Web of Science, EMBASE, Cochrane databases, and Google Scholar using relevant keywords. A fix or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Twelve RCTs were included in the present meta-analysis. The pooled analysis revealed that serum concentrations of CRP (WMD: -0.59 mg/L, 95% CI -0.85 to -0.33, p < 0.001) were significantly reduced following folic acid supplementation compared to placebo, but did not affect serum concentrations of IL-6 (WMD: -0.12, 95% CI -0.95 to 0.72 pg/mL, p = 0.780) or TNF-α (WMD: -0.18, 95% CI -0.86 to 0.49 pg/mL, p = 0.594). The dose-response analysis demonstrated a significant relationship between an elevated dosage of folic acid supplementation and lower CRP concentrations (p = 0.002). Conclusions: We found that folic acid supplementation may improve inflammation by attenuating serum concentrations of CRP but without significant effects on IL-6 and TNF-α. Future RCTs including a larger number of participants and more diverse populations are needed to confirm and expand our findings.