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1.
New insights into molecular pathways in colorectal cancer: Adiponectin, interleukin-6 and opioid signaling.
Świerczyński, M, Szymaszkiewicz, A, Fichna, J, Zielińska, M
Biochimica et biophysica acta. Reviews on cancer. 2021;(1):188460
Abstract
Colorectal cancer (CRC) is one of the most common cause of death among neoplasms around the world. The environmental factors, like diet and obesity, are crucial in CRC pathogenesis by creating cancer-favorable microenvironment and hormonal changes. Adiponectin, the adipose tissue-specific hormone, is generally considered to negatively correlate with CRC development. The interleukin 6 (IL-6) is one of the most important pro-inflammatory cytokine connected with CRC, which is strongly inflammation-associated. The opioids are variable group substantially correlated with cancers - the endogenous opioids affect immune system and cell cycle including proliferation and cell death whereas exogenous opioids are leading clinically used analgesics in terminal cancer patients. In this review we discuss the involvement of adiponectin, IL-6 and opioids in CRC pathogenesis, their link with obesity, possible cross-talk and potential novel therapeutic approach in CRC treatment.
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2.
Association between diabetic retinopathy and interleukin-related gene polymorphisms: a machine learning aided meta-analysis.
Sun, X, Guo, S
Ophthalmic genetics. 2020;(3):216-222
Abstract
BACKGROUND Diabetic retinopathy (DR) is a severe complication of diabetes and a common cause of visual loss in adults. We aimed to assess the correlation between IL gene-related SNPs and the incidence of DR and attempted to predict DR with combined mutation site detection. METHODS A systematic search of databases was performed up to August 2019. Five genetic models were used to analyze associations. Machine learning methods were implemented to improve SNP-related disease prediction. RESULTS Sixteen trials assessing a total of 7221 patients were included in our meta-analysis. IL6/rs1800795, rs1800796, and IL10/rs1800896 were analyzed. For the IL-6 gene, there was no significant association between rs1800795 and the incidence of DR (allelic model: OR, 1.091; 95% CI, 0.892-1.334; p = .396). There was no significant correlation between rs1800796 (allelic model: OR, 1.135; 95% CI, 0.678-1.901; p = .63), rs1800896 (allelic model: OR, 1.047; 95% CI, 0.788-1.392; p = .752) and the incidence of DR. Unfortunately, the machine learning results also showed that the combined detection of two SNPs could not accurately predict DR occurrence. CONCLUSION rs1800795 and rs1800796 in the IL-6 gene and rs1800896 in IL-10 gene are not related to the incidence of DR. Mutations in multiple SNPs for each DR patient still need to be specifically assessed to increase prediction accuracy.
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3.
The association of interieukin-6 polymorphism (rs1800795) with microvascular complications in Type 2 diabetes mellitus.
Cui, J, Zhang, X, Guo, C, Zhang, L
Bioscience reports. 2020;(10)
Abstract
OBJECTIVES To evaluate the effects of the single-nucleotide polymorphism (SNP) rs1800795 in interieukin-6 (IL-6) gene on diabetic microvascular complications of Type 2 diabetes mellitus (T2DM), using statistical meta-analysis. METHODS Literature pertaining to the relationship between the SNP rs1800795 and microvascular complications of T2DM including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and foot disease was retrieved from PubMed, Web of Science Knowledge and SinoMed databases. Original information was analyzed using Stata 12.0, including meta-analysis statistics, test for heterogeneity, evaluation of publication bias and sensitivity. Subgroup analysis was conducted to assess the effect of specific factors on the corresponding results. RESULTS In total, 14 eligible articles were obtained. The SNP rs1800795 in IL-6 gene is not correlated with risk of microvascular complications in T2DM. Among the original literature, a genetic model (OR = 1.071, 95% CI: 0.681-1.685, P=0.767), an allelic genetic model (OR = 1.010, 95% CI: 0.959-1.063, P=0.703), a heterozygote genetic model (OR = 1.107, 95% CI: 0.916-1.339, P=0.292), a dominant genetic model (OR = 1.108, 95% CI: 0.885-1.387, P=0.372), and a recessive genetic model (OR = 0.978, 95% CI: 0.646-1.478, P=0.917) were included respectively. In the subgroup analysis by types of diabetic microvascular complications, we found no correlation between the SNP rs1000795 polymorphism and complications of T2DM in either the homozygote genetic model or the allelic genetic model (P<0.05). CONCLUSION Our results demonstrate that rs1800795 polymorphism in IL-6 gene is not correlated with the susceptibility of microvascular complications of T2DM.
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4.
Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.
Zhai, J, Bo, Y, Lu, Y, Liu, C, Zhang, L
PloS one. 2017;(1):e0170172
Abstract
BACKGROUND/OBJECTIVE Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10) has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases. METHODS Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs). The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C reactive protein (CRP). RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software. RESULTS Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87) μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24) pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17) mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16) pg/ml, I2 = 84%]. CONCLUSIONS CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.
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5.
Nutritional interventions and the IL-6 response to exercise.
Hennigar, SR, McClung, JP, Pasiakos, SM
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2017;(9):3719-3728
Abstract
IL-6 is a pleiotropic cytokine with a wide range of biologic effects. In response to prolonged exercise, IL-6 is synthesized by contracting skeletal muscle and released into circulation. Circulating IL-6 is thought to maintain energy status during exercise by acting as an energy sensor for contracting muscle and stimulating glucose production. If tissue damage occurs, immune cells infiltrate and secrete cytokines, including IL-6, to repair skeletal muscle damage. With adequate rest and nutrition, the IL-6 response to exercise is attenuated as skeletal muscle adapts to training. However, sustained elevations in IL-6 due to repeated bouts of unaccustomed activities or prolonged exercise with limited rest may result in untoward physiologic effects, such as accelerated muscle proteolysis and diminished nutrient absorption, and may impair normal adaptive responses to training. Recent intervention studies have explored the role of mixed meals or carbohydrate, protein, ω-3 fatty acid, or antioxidant supplementation in mitigating exercise-induced increases in IL-6. Emerging evidence suggests that sufficient energy intake before exercise is an important factor in attenuating exercise-induced IL-6 by maintaining muscle glycogen. We detail various nutritional interventions that may affect the IL-6 response to exercise in healthy human adults and provide recommendations for future research exploring the role of IL-6 in the adaptive response to exercise.-Hennigar, S. R., McClung, J. P., Pasiakos, S. M. Nutritional interventions and the IL-6 response to exercise.
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6.
Association Between IL6-174 G/C Polymorphism and Graves' Disease: A Systematic Review and Meta-Analysis.
Imani, D, Rezaei, R, Razi, B, Alizadeh, S, Mahmoudi, M
Acta medica Iranica. 2017;(11):665-671
Abstract
Several studies have evaluated the association between interleukin-6 (IL-6) -174 G/C polymorphism and Graves' disease (GD); however, the results have been inconsistent. In the current study, a meta-analysis was performed to assess the association of IL6 -174 G/C polymorphism with Graves' disease. Medline, EMBASE, and Web of Science databases were searched to identify all eligible studies published before August 2016. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to assess the strength of association in dominant, recessive, allelic, homozygotes contrast, and heterozygotes contrast models. A total of four case-control studies with 554 GD cases and 1201 healthy controls were included in this meta-analysis. In the combined analysis, the results showed significant association between the IL6 -174 G/C polymorphism and the risk for GD in dominant model (OR=1.39, 95% CI: 1.07-1.80), recessive model (OR=2.75, 95% CI: 1.01-7.55) and homozygote contrast model (OR=3.25, 95% CI: 1.1-9.58). No publication bias was found in the current study (all P>0.05). The meta-analysis results suggested that the IL6 -174 G/C polymorphism was indicated to be associated with the risk of GD. Further studies are warranted to confirm these results.
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7.
A narrative review of the associations between six bioactive components in breast milk and infant adiposity.
Fields, DA, Schneider, CR, Pavela, G
Obesity (Silver Spring, Md.). 2016;(6):1213-21
Abstract
OBJECTIVE This narrative review examines six important non-nutritive substances in breast milk, many of which were thought to have little to no biological significance. The overall objective is to provide background on key bioactive factors in breast milk believed to have an effect on infant outcomes (growth and body composition). METHODS The evidence for the effects of the following six bioactive compounds in breast milk on infant growth outcomes are reviewed: insulin, leptin, adiponectin, ghrelin, interleukin-6, and tumor necrosis factor-α. RESULTS The existing literature on the effects of breast milk insulin, ghrelin, interleukin-6, and tumor necrosis factor-α and their associations with infant growth and adiposity is sparse. Of the bioactive compounds reviewed, leptin and adiponectin are the most researched. Data reveal that breast milk adiponectin has negative associations with growth in infancy. CONCLUSIONS There is a need for innovative, well-designed studies to improve causal inference and advance our understanding in the effects of breast milk and its components on offspring growth and body composition. The recommendations provided, along with careful consideration of both known and unknown factors that affect breast milk composition, will help improve, standardize, and ultimately advance this emergent field.
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8.
[Anemic syndrome in rheumatoid arthritis: Diagnostic approaches and treatment opportunities].
Grinshtein, YI, Shabalin, VV, Kusaev, VV
Terapevticheskii arkhiv. 2016;(5):107-112
Abstract
Anemia of chronic disease (ACD) is a leading cause of anemic syndrome in patients with rheumatoid arthritis (RA). Enhanced hepcidin production mainly stimulated by excess interleukin-6 levels is a key pathodgentic component of ACD (frequently known as anemia of inflammation) by causing the degradation of the transmembrane protein ferroportin, hepcidin impairs iron metabolism. On the basis of the material of recent publications the review gives present-day views on the pathodgenesis of ACD in RA, approaches to the diagnosis and differential diagnosis of ACD, especially in its concomitance with iron-deficiency anemia, as well as approaches to therapy for the type of anemic syndrome with the complex mechanism for its development.
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Effect of nutritional status and dietary patterns on human serum C-reactive protein and interleukin-6 concentrations.
Smidowicz, A, Regula, J
Advances in nutrition (Bethesda, Md.). 2015;(6):738-47
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Abstract
The inflammatory process plays an important role in the pathogenesis of many chronic diseases, such as cardiovascular diseases, diabetes mellitus type 2, and metabolic syndrome. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) are widely tested inflammatory markers involved in the development of these diseases. Several studies indicate a relation between nutritional status and the concentrations of human high-sensitivity CRP and IL-6. Similarly, the role of diet in reducing inflammation and thereby modulating the risk of non-communicable diseases is supported by numerous studies. This review focuses on the effects of the selected nutrition models in humans on the concentrations of CRP and IL-6. It seems that the Mediterranean diet model is most effective in inhibiting inflammation. The Dietary Approaches to Stop Hypertension model and the plant nutrition model also have proven to be beneficial. The data on low-fat and low-carbohydrate diets are inconclusive. Comprehensive studies are necessary, taking into account the cumulative effect of dietary and other factors on the inflammatory process.
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Transcriptome and Molecular Endocrinology Aspects of Epicardial Adipose Tissue in Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Observational Studies.
Maghbooli, Z, Hossein-Nezhad, A
BioMed research international. 2015;:926567
Abstract
The objective of this study was to perform a systematic review of published literature on differentially expressed genes (DEGs) in human epicardial adipose tissue (EAT) to identify molecules associated with CVDs. A systematic literature search was conducted in PubMed, SCOPUS, and ISI Web of Science literature databases for papers published before October 2014 that addressed EAT genes and cardiovascular diseases (CVDs). We included original papers that had performed gene expressions in EAT of patients undergoing open-heart surgery. The Reporting Recommendations for Tumor Marker Prognostic Studies (PRIMARK) assessment tool was also used for methodological quality assessment. From the 180 papers identified by our initial search strategy, 40 studies met the inclusion criteria and presented DEGs in EAT samples from patients with and without CVDs. The included studies reported 42 DEGs identified through comparison of EAT-specific gene expression in patients with and without CVDs. Among the 42 DEGs, genes involved in regulating apoptosis had higher enrichment scores. Notably, interleukin-6 (IL-6) and tumor protein p53 (TP53) were the main hub genes in the network. The results suggest that regulation of apoptosis in EAT is critical for CVD development. Moreover, IL-6 and TP53 as hub genes could serve as biomarkers and therapeutic targets for CVDs.