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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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Assessment of a 4-Week Starch- and Sucrose-Reduced Diet and Its Effects on Gastrointestinal Symptoms and Inflammatory Parameters among Patients with Irritable Bowel Syndrome.
Nilholm, C, Larsson, E, Sonestedt, E, Roth, B, Ohlsson, B
Nutrients. 2021;(2)
Abstract
Dietary advice constitutes a treatment strategy for irritable bowel syndrome (IBS). We aimed to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal symptoms in IBS patients, in relation to dietary intake and systemic inflammatory parameters. IBS patients (n = 105) were randomized to a 4-week SSRD intervention (n = 80) receiving written and verbal dietary advice focused on starch and sucrose reduction and increased intake of protein, fat and dairy, or control group (n = 25; habitual diet). At baseline and 4 weeks, blood was sampled, and participants filled out IBS-SSS, VAS-IBS, and Rome IV questionnaires and dietary registrations. C-reactive protein and cytokines TNF-α, IFN-γ, IL-6, IL-8, IL-10, and IL-18 were analyzed from plasma. At 4 weeks, the intervention group displayed lower total IBS-SSS, 'abdominal pain', 'bloating/flatulence' and 'intestinal symptoms´ influence on daily life' scores (p ≤ 0.001 for all) compared to controls, and a 74%, responder rate (RR = ΔTotal IBS-SSS ≥ -50; RRcontrols = 24%). Median values of sucrose (5.4 vs. 20 g), disaccharides (16 vs. 28 g), starch (22 vs. 82 g) and carbohydrates (88 vs. 182 g) were lower for the intervention group compared to controls (p ≤ 0.002 for all), and energy percentages (E%) of protein (21 vs. 17 E%, p = 0.006) and fat (47 vs. 38 E%, p = 0.002) were higher. Sugar-, starch- and carbohydrate-reductions correlated weakly-moderately with total IBS-SSS decrease for all participants. Inflammatory parameters were unaffected. IBS patients display high compliance to the SSRD, with improved gastrointestinal symptoms but unaltered inflammatory parameters. In conclusion, the SSRD constitutes a promising dietary treatment for IBS, but needs to be further researched and compared to established dietary treatments before it could be used in a clinical setting.
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The design and discovery of phospholipase A2 inhibitors for the treatment of inflammatory diseases.
Batsika, CS, Gerogiannopoulou, AD, Mantzourani, C, Vasilakaki, S, Kokotos, G
Expert opinion on drug discovery. 2021;(11):1287-1305
Abstract
AREAS COVERED This review article summarizes the most important synthetic PLA2 inhibitors developed to target each one of the four major types of human PLA2 (cytosolic cPLA2, calcium-independent iPLA2, secreted sPLA2, and lipoprotein-associated Lp-PLA2), discussing their in vitro and in vivo activities as well as their recent applications and therapeutic properties. Recent findings on the role of PLA2 in the pathobiology of COVID-19 are also discussed. EXPERT OPINION Although a number of PLA2 inhibitors have entered clinical trials, none has reached the market yet. Lipoprotein-associated PLA2 is now considered a biomarker of vascular inflammation rather than a therapeutic target for inhibitors like darapladib. Inhibitors of cytosolic PLA2 may find topical applications for diseases like atopic dermatitis and psoriasis. Inhibitors of secreted PLA2, varespladib and varespladib methyl, are under investigation for repositioning in snakebite envenoming. A deeper understanding of PLA2 enzymes is needed for the development of novel selective inhibitors. Lipidomic technologies combined with medicinal chemistry approaches may be useful tools toward this goal.
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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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Human gut-microbiome interplay: Analysis of clinical studies for the emerging roles of diagnostic microbiology in inflammation, oncogenesis and cancer management.
Jiang, Z, Li, L, Chen, J, Wei, G, Ji, Y, Chen, X, Liu, J, Huo, J
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2021;:104946
Abstract
Microorganisms have been known to coexist in various parts of human body including the gut. The interactions between microbes and the surrounding tissues of the host are critical for fine fettle of the gut. The incidence of such microorganisms tends to vary among specific type of cancer affected individuals. Such microbial communities of specific tumor sites in cancer affected individuals could plausibly be used as prognostic and/or diagnostic markers for tumors associated with that specific site. Microorganisms of intestinal and non-intestinal origins including Helicobacter pylori can target several organs, act as carcinogens and promote cancer. It is interesting to note that diets causing inflammation can also increase the cancer risk. Yet, dietary supplementation with prebiotics and probiotics can reduce the incidence of cancer. Therefore, both diet and microbial community of the gut have dual roles of prevention and oncogenesis. Hence, this review intends to summarize certain important details related to gut microbiome and cancer.
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Effects of curcuminoids on inflammatory and oxidative stress biomarkers and clinical outcomes in critically ill patients: A randomized double-blind placebo-controlled trial.
Zahedi, H, Hosseinzadeh-Attar, MJ, Shadnoush, M, Sahebkar, A, Barkhidarian, B, Sadeghi, O, Najafi, A, Hosseini, S, Qorbani, M, Ahmadi, A, et al
Phytotherapy research : PTR. 2021;(8):4605-4615
Abstract
Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU-admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL-6, TNF-α, MCP-1 and CRP were significantly reduced in patients receiving curcuminoids (p < .05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p < .05). The findings of this study suggest that short-term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI.
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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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Use of Cytokine Mix-, Imiquimod-, and Serum-Induced Monoculture and Lipopolysaccharide- and Interferon Gamma-Treated Co-Culture to Establish In Vitro Psoriasis-like Inflammation Models.
Bocheńska, K, Moskot, M, Gabig-Cimińska, M
Cells. 2021;(11)
Abstract
Psoriasis (Ps), commonly perceived as a skin and joint disorder, has a complex basis and results from disturbances in the sophisticated network between skin and the immune system. This makes it difficult to properly depict the complete pathomechanism on an in vitro scale. Deciphering the complicated or even subtle modulation of intra- and intercellular factors, assisted by the implementation of in vitro human skin models, may provide the opportunity to dissect the disease background step by step. In addition to reconstructed artificial skin substitutes, which mimic the native physiological context, in vitro models are conducive to the broad "3 Rs" philosophy (reduce, refine, and replace) and represent important tools for basic and applied skin research. To meet the need for a more comprehensive in vitro Ps model, a set of various experimental conditions was applied in this study. The selection of in vitro treatment that mimicked the Ps phenotype was illustrated by analyses of discriminating biomarker genes involved in the pathogenesis of the disease, i.e., keratinocyte differentiation markers, antimicrobial peptides, chemokines, and proliferation markers. This resulted in a reproducible protocol for the use of the primary skin keratinocyte (pKC) monoculture treated with a cytokine cocktail (5MIX, i.e., interleukin (IL) 1 alpha (IL-1α), IL-17A, IL-22, oncostatin M (OSM), and tumour necrosis factor alpha (TNF-α)) at a calcium (Ca2+) concentration (i.e., 2 mM) in an applied medium, which best mirrored the in vitro Ps-like inflammatory model. In addition, based on waste skin material, the method has the potential for extensive experimentation, both in detailed molecular studies and preclinical tests.
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Strategies to DAMPen COVID-19-mediated lung and systemic inflammation and vascular injury.
Bime, C, Casanova, NG, Nikolich-Zugich, J, Knox, KS, Camp, SM, Garcia, JGN
Translational research : the journal of laboratory and clinical medicine. 2021;:37-48
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Abstract
Approximately 15%-20% of patients infected with SARS-CoV-2 coronavirus (COVID-19) progress beyond mild and self-limited disease to require supplemental oxygen for severe pneumonia; 5% of COVID-19-infected patients further develop acute respiratory distress syndrome (ARDS) and multiorgan failure. Despite mortality rates surpassing 40%, key insights into COVID-19-induced ARDS pathology have not been fully elucidated and multiple unmet needs remain. This review focuses on the unmet need for effective therapies that target unchecked innate immunity-driven inflammation which drives unchecked vascular permeability, multiorgan dysfunction and ARDS mortality. Additional unmet needs including the lack of insights into factors predicting pathogenic hyperinflammatory viral host responses, limited approaches to address the vast disease heterogeneity in ARDS, and the absence of clinically-useful ARDS biomarkers. We review unmet needs persisting in COVID-19-induced ARDS in the context of the potential role for damage-associated molecular pattern proteins in lung and systemic hyperinflammatory host responses to SARS-CoV-2 infection that ultimately drive multiorgan dysfunction and ARDS mortality. Insights into promising stratification-enhancing, biomarker-based strategies in COVID-19 and non-COVID ARDS may enable the design of successful clinical trials of promising therapies.
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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).