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Changes in aqueous and vitreous inflammatory cytokine levels in diabetic macular oedema: a systematic review and meta-analysis.
Minaker, SA, Mason, RH, Lahaie Luna, G, Farahvash, A, Garg, A, Bhambra, N, Bapat, P, Muni, RH
Acta ophthalmologica. 2022;(1):e53-e70
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Abstract
Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p-value) of aqueous IL-6 (1.28, 0.57-2.00, p = 0.004), IL-8 (1.06, 0.74-1.39, p < 0.00001), MCP-1 (1.36, 0.57-2.16, p = 0.0008) and VEGF (1.31, 1.01-1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55-2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms.
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Effect of resistant starch type 2 on inflammatory mediators: A systematic review and meta-analysis of randomized controlled trials.
Haghighatdoost, F, Gholami, A, Hariri, M
Complementary therapies in medicine. 2021;:102597
Abstract
BACKGROUND Inflammation is the main cause in the development of chronic diseases. The enhancement of pro-inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) is the main risk factor in chronic diseases. Resistant starch type 2 (RS2) is non-gelatinized granules which their enzymatic hydrolysis is very low. RS2 might be able to reduce inflammatory mediators, therefore; our aim for this study was indicating RS2 effects on inflammatory mediators such as IL-6, TNF-a, and CRP among healthy and unhealthy subjects. METHODS Articles which assessed RS2 effect on IL-6, TNF-α, and hs-CRP were found by advanced search methods. Electronic databases including Google scholar, ISI web of science, SCOPUS, and PubMed, were searched up to October 2019. Treatment effect was the mean difference between changes in serum levels of inflammatory biomarkers in each arm of the clinical trials. To pool the effect of resistant starch on inflammatory biomarkers, we used random effects model. RESULTS We included eight articles in systematic review and meta-analysis. The overall effect illustrated no significant change in serum levels of hs-CRP, IL-6, and TNF-α in intervention group compared with the control group (WMD: -7.18 pg/mL, 95% CI: -27.80, 13.45; P = 0.495, I2 = 100.0%, WMD: -0.003 pg/mL, 95% CI: -0.07, 0.06; P = 0.919, I2 = 98.1%, WMD: -0.003 pg/mL, 95% CI: -0.004, -0.001; P < 0.0001, I2 = 98.0% respectively). CONCLUSION In conclusion, we found that RS2 could not reduce inflammatory mediators, but we still need more RCTs with longer intervention duration, higher dose, and studies in different countries.
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Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta-analysis.
Asbaghi, O, Sadeghian, M, Sadeghi, O, Rigi, S, Tan, SC, Shokri, A, Mousavi, SM
Phytotherapy research : PTR. 2021;(1):20-32
Abstract
The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta-analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF-α, and IL-6 were included. For each outcome, mean differences and SDs were pooled using a random-effects model. Overall, eight RCTs were included in this meta-analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: -0.43 mg/L; 95% confidence interval [CI]: -1.04 to 0.17; p = .16), serum TNF-α (WMD: -1.29 pg/mL; 95% CI: -4.13 to 1.55; p = .37), and IL-6 concentrations (WMD: 0.11 pg/mL; 95% CI: -0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF-α in studies that recruited non-diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non-linear effect of saffron dosage on serum CRP concentrations (pnon-linearity = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high-quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.
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Effects of grape products on inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.
Ghalishourani, SS, Farzollahpour, F, Shirinbakhshmasoleh, M, Kolahdouz, S, Ghaedi, E, Behrouzian, M, Haghighian, HK, Campbell, MS, Asbaghi, O, Moodi, V
Phytotherapy research : PTR. 2021;(9):4898-4912
Abstract
This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to determine the effects of grapes and grape products on inflammation and oxidative stress among adults. PubMed, Scopus, ISI Web of Science, and Cochrane Library databases were searched up to July 2020 to identify RCTs investigating the effects of grape and grape products on inflammatory and oxidative stress markers. Weighted mean differences (WMD) were pooled using a random-effects model. Of the 8,962 identified studies, 24 RCTs (27 arms) were included in the statistical analysis. Grape products significantly reduced serum C-reactive protein (CRP) levels (WMD: -0.35 mg/L; 95% CI: -0.62, -0.09, p = .008), but they had no significant effect on serum tumor necrosis factor-alpha (TNF-α) (WMD = -1.08 pg/ml; 95% CI: -2.29, 0.11, p = .07), interleukin-6 (IL-6) (WMD = 0.13 pg/ml; 95% CI: -0.35, 0.60, p = .60), total antioxidant capacity (TAC) (WMD = 0.15; 95% CI: -0.35, 0.65, p = .54), or malondialdehyde (MDA) (WMD = 0.14; 95% CI: -0.64, 0.92, p = .72). The analysis indicated possible decreasing effects of grapes and grape products on CRP, but they might not be able to change IL-6, TNF-α, TAC, and MDA concentrations. Nonetheless, further studies are warranted before definitive conclusions may be reached.
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The Effects of Almonds on Gut Microbiota, Glycometabolism, and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
Ojo, O, Wang, XH, Ojo, OO, Adegboye, ARA
Nutrients. 2021;(10)
Abstract
UNLABELLED The use of nutritional interventions for managing diabetes is one of the effective strategies aimed at reducing the global prevalence of the condition, which is on the rise. Almonds are the most consumed tree nut and they are known to be rich sources of protein, monounsaturated fatty acids, essential minerals, and dietary fibre. Therefore, the aim of this review was to evaluate the effects of almonds on gut microbiota, glycometabolism, and inflammatory parameters in patients with type 2 diabetes. METHODS This systematic review and meta-analysis was carried out according to the preferred reporting items for systematic review and meta-analysis (PRISMA). EBSCOhost, which encompasses the Health Sciences Research Databases; Google Scholar; EMBASE; and the reference lists of articles were searched based on population, intervention, control, outcome, and study (PICOS) framework. Searches were carried out from database inception until 1 August 2021 based on medical subject headings (MesH) and synonyms. The meta-analysis was carried out with the Review Manager (RevMan) 5.3 software. RESULTS Nine randomised studies were included in the systematic review and eight were used for the meta-analysis. The results would suggest that almond-based diets have significant effects in promoting the growth of short-chain fatty acid (SCFA)-producing gut microbiota. Furthermore, the meta-analysis showed that almond-based diets were effective in significantly lowering (p < 0.05) glycated haemoglobin (HbA1c) levels and body mass index (BMI) in patients with type 2 diabetes. However, it was also found that the effects of almonds were not significant (p > 0.05) in relation to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and Tumour necrosis factor α, TNF-α), glucagon-like peptide-1 (GLP-1), homeostatic model assessment of insulin resistance (HOMA-IR), and fasting insulin. The biological mechanisms responsible for the outcomes observed in this review in relation to reduction in HbA1c and BMI may be based on the nutrient composition of almonds and the biological effects, including the high fibre content and the low glycaemic index profile. CONCLUSION The findings of this systematic review and meta-analysis have shown that almond-based diets may be effective in promoting short-chain fatty acid-producing bacteria and lowering glycated haemoglobin and body mass index in patients with type 2 diabetes compared with control. However, the effects of almonds were not significant (p > 0.05) with respect to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and TNF-α), GLP-1, HOMA-IR, and fasting insulin.
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A posteriori dietary patterns and their association with systemic low-grade inflammation in adults: a systematic review and meta-analysis.
Norde, MM, Collese, TS, Giovannucci, E, Rogero, MM
Nutrition reviews. 2021;(3):331-350
Abstract
CONTEXT A posteriori dietary patterns are promising ways of uncovering potential public health strategies for the prevention of systemic, low-grade, inflammation-related, chronic noncommunicable diseases. OBJECTIVE To investigate and summarize the current evidence on the association between a posteriori dietary patterns and systemic, low-grade inflammation in adults. DATA SOURCES MEDLINE, EMBASE, Web of Science, and LILACS were searched. DATA EXTRACTION Data screening, extraction, and quality assessment were performed independently by 2 investigators. Meta-analysis with random effects was conducted. Differences and similarities between reduced rank regression-derived dietary patterns were assessed. RESULTS Healthy dietary patterns are inversely and the Western dietary pattern is positively associated with inflammation (r = -0.13, 95% confidence interval -0.20 to -0.06; and r = 0.11, 95% confidence interval, 0.09-0.12, respectively). Reduced rank regression-derived anti-inflammatory dietary patterns are consistently characterized by high intake of fresh fruits and inflammatory dietary patterns are consistently characterized by high intake of red and processed meat and low intake of vegetables. CONCLUSION Favoring the substitution of a Westernized diet for a healthy diet may lower inflammation, which might improve the prevention of some chronic noncommunicable diseases.
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Beneficial Effects of Vitamin E Supplementation on Endothelial Dysfunction, Inflammation, and Oxidative Stress Biomarkers in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Nguyen, TTU, Yeom, JH, Kim, W
International journal of molecular sciences. 2021;(21)
Abstract
Inflammation and oxidative stress are closely related to cardiovascular complications and atherosclerosis, and have the potential to lead to an increase in death in patients receiving hemodialysis. Vitamin E has antioxidant and anti-inflammatory properties. We conducted a systematic review and meta-analysis to assess the effects of vitamin E supplementation on endothelial dysfunction, inflammation, and oxidative stress biomarkers in adult patients receiving hemodialysis. We searched the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases and identified randomized controlled trials of adult patients receiving hemodialysis until 30 August 2021. A total of 11 trials with 491 randomized patients were included. The pooled data indicated that vitamin E supplementation significantly decreased intercellular adhesion molecule-1 [standardized mean difference (SMD): -1.35; 95% confidence interval (CI): -2.57, -0.13; p = 0.03, I2 = 89%], vascular cell adhesion molecule-1 (SMD: -1.08; 95% CI: -2.05, -0.11; p = 0.03, I2 = 81%), C-reactive protein (SMD: -0.41; 95% CI: -0.75, -0.07; p = 0.02, I2 = 64%), and malondialdehyde (SMD: -0.76; 95% CI: -1.26, -0.25; p = 0.003, I2 = 77%) levels, but not interleukin-6 levels compared to those in the control group. Our results suggest that vitamin E supplementation may help alleviate oxidative stress and both vascular and systemic inflammation in patients receiving hemodialysis.
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Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.
Hosseini, R, Ferns, GA, Sahebkar, A, Mirshekar, MA, Jalali, M
Cytokine. 2021;:155396
Abstract
BACKGROUND Zinc (Zn) is a trace metal that is considered to have an impact on chronic inflammation. However, findings of clinical trials have been inconsistent. The present systematic review and meta-analysis aimed to provide a more robust examination of the evidence on the effectiveness of Zn supplements on markers of inflammation and oxidative stress. METHODS A systematic search in PubMed, Scopus, Web of Science and Cochrane Library was undertaken to identify relevant randomized controlled trials (RCTs) assessing the impact of Zn on inflammation and oxidative stress until 17 August 2020. We applied a random-effects method to obtain effect sizes (ES) and 95% confidence intervals (CIs). Meta-regression was used to detect the potential source of between-study heterogeneity. RESULTS Twenty-one eligible RCTs comprising 1321 participants were included in the meta-analysis. In comparison with the control groups, serum C-reactive protein (CRP) (ES = -0.92 mg/L, 95% CI = [-1.36, -0.48], P < 0.001, I2 = 90.2%), tumor necrosis factor-alpha (TNF-α) (ES = -0.49 pg/mL, 95% CI = [-084, -0.14], P = 0.006, I2 = 34.6%) and malondialdehyde (MDA) (ES = -0.42, 95% CI = [-083, -0.01], P = 0.04, I2 = 76.1%) were significantly reduced in the groups receiving Zn. Serum interleukin 6 (ES = -1.02 pg/mL, 95% CI = [-2.06, 0.02], P = 0.05, I2 = 92.3%) was marginally reduced following Zn supplementation. Moreover, treatment duration was found as the source of inter-study heterogeneity. CONCLUSION This meta-analysis suggests that Zn supplements reduce serum concentrations of markers of inflammation and oxidation: CRP, TNF-α and MDA.
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The effect of Nigella sativa on oxidative stress and inflammatory biomarkers: a systematic review and meta-analysis.
Malekian, S, Ghassab-Abdollahi, N, Mirghafourvand, M, Farshbaf-Khalili, A
Journal of complementary & integrative medicine. 2021;(2):235-259
Abstract
OBJECTIVES The present systematic review of literature was conducted to study the effect of Nigella sativa (N.S) on oxidative stress and inflammatory biomarkers. CONTENT Different online databases such as Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), Scopus, Web of Sciences, EMBASE, and Clininaltrial.gov for English articles and national databases of SID, Magiran, Irandoc, and Iranmedex for Persian articles, which were published until March; 2019 were scrutinized. All Randomised Controlled Trials (RCTs) and quasi-experimental studies that aimed to compare the impact of N.S along, with placebo or without supplementation, on inflammatory factors and oxidative stress were entered in the present study. SUMMARY Finally, 11 RCTs covering 710 women and men, in total, were participated in the present meta-analysis. Significant differences were observed in Tumor Necrosis Factor alpha (TNF-α) (Weighted Mean Difference (WMD) =-2.15 pg/mL, 95% Confidence Interval (CI) =-3.22--1.09, I2=32%; 5 trials with 262 participants) superoxide dismutase (WMD=63.79 µ/gHb, 95% CI=6.84-120.75, I2=0%; 2 trials, with 88 participants), and total antioxidant capacity (WMD=0.34 mmol/L, 95% CI=0.04 to 0.63, I2=94%; 5 trials with 232 participants). Nevertheless, there was no significant difference in high sensitivity C-reactive protein (WMD=-0.98 mg/L, 95% CI=-1.98-0.03, I2=78%; 5 trials with 267 participants), Interleukin 6 (IL-6) (WMD=-0.25 pg/mL, 95% CI=-0.65 to 0.16, I2=0%; 2 trials with 134 participants), and malondialdehyde (WMD=-0.95 nmol/mL, 95% CI=-1.97-0.08, I2=68%; 4 trials with 179 participants). OUTLOOK Generally speaking, N.S probably results in the improvement of superoxide dismutase serum levels, TNF-α, and total antioxidant capacity. Thus, further studies are required to fully assess its impacts on all oxidative stress and inflammatory biomarkers.
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The effect of exercise intensity on chronic inflammation: A systematic review and meta-analysis.
Rose, GL, Skinner, TL, Mielke, GI, Schaumberg, MA
Journal of science and medicine in sport. 2021;(4):345-351
Abstract
OBJECTIVES Chronic inflammation is independently associated with the incidence and progression of chronic disease. Exercise has been found to reduce chronic inflammation, however the role of exercise intensity (work rate) is unknown. This review aimed to determine the pooled effect of higher- compared to lower-intensity aerobic and resistance exercise on chronic inflammation in adults. DESIGN Systematic review and meta-analysis. METHODS Five electronic databases were searched. Intervention trials that assessed the effect of ≥2 different exercise intensities on peripheral markers of chronic inflammation [c-reactive protein (CRP), interleukin (IL)-6, tumour necrosis factor (TNF)-α and IL-10] in adults were included. Random-effect meta-analyses were conducted to calculate the mean difference in change scores between groups [effect size (ES)]. Sub-group analyses were performed to explore the influence of age, chronic disease, body mass index and intervention duration on inflammation heterogeneity. RESULTS Of 3952 studies identified, 27 were included. There were no significant effects of exercise intensity on IL-6 (ES=-0.039, 95%CI=-0.353-0.275; p=0.806), TNF-α (ES=0.296, 95%CI=-0.184-0.777; p=0.227) and IL-10 (ES=0.007, 95%CI=-0.904-0.919; p=0.987). A significant pooled ES was observed for higher- versus lower-intensity exercise on CRP concentrations, in studies of middle-aged adults (ES=-0.412, 95%CI=-0.821- -0.004, p=0.048) or interventions >9 weeks in duration (ES=-0.520, 95%CI=-0.882--0.159, p=0.005). CONCLUSIONS Exercise intensity did not influence chronic inflammatory response. However, sub-analyses suggest that higher-intensity training may be more efficacious than lower-intensity for middle-aged adults, or when longer duration interventions are implemented (>9 weeks), in the most commonly-reported analyte (CRP).