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The effect of glutamine supplementation on serum levels of some inflammatory factors, oxidative stress, and appetite in COVID-19 patients: a case-control study.
Mohajeri, M, Horriatkhah, E, Mohajery, R
Inflammopharmacology. 2021;(6):1769-1776
Abstract
BACKGROUND Malnutrition is seen in COVID-19 patients, and reducing malnutrition with appropriate therapies may improve these patients' health. This case-control study aimed to assess and compare serum levels of some inflammatory factors, oxidative stress, and appetite in COVID-19 patients with respiratory infections that receive glutamine treatment with a control group. METHODS In this study, patients who consented to use glutamine were considered as the case group and other patients who did not use glutamine were considered as a control group. Two hundred twenty-two COVID-19 patients (51.2 ± 6.7) using L-Glutamine and 230 COVID-19 patients (51.3 ± 8.2) with similar age, gender, and clinical status, as the control group, were included in the study. For 5 days, the case group consumed 10 g of glutamine supplement three times per day. At the end of the 5 days, blood samples were taken again to test for serum levels of IL1β, tumor necrosis factor-α, malondialdehyde, and total antioxidant capacity, then all data were analyzed. RESULTS Serum levels of β-1 interleukin, tumor necrosis factor-α and hs-CRP were significantly reduced with five days of glutamine supplementation (p < 0.05), and patients' appetite during 5 days of glutamine supplementation compared with the control group had a significant increase (p < 0.05). CONCLUSION Glutamine supplementation in COVID-19 patients with respiratory infection significantly reduces serum levels of interleukin-1 β, hs-CRP, and tumor necrosis factor-α and significantly increases appetite, so glutamine supplementation may be useful for COVID-19 patients in the hospital.
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TNFα Mediates the Interaction of Telomeres and Mitochondria Induced by Hyperglycemia: A Rural Community-Based Cross-Sectional Study.
Lyu, L, He, S, Zhang, H, Li, W, Zeng, J, Ping, F, Li, YX
Oxidative medicine and cellular longevity. 2020;:8235873
Abstract
This study is aimed at evaluating the relationship between leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in a noninterventional rural community of China with different glucose tolerance statuses. In addition, we investigate whether the indicators of oxidative stress and inflammation were involved and identify mediators among them. A total of 450 subjects in rural China were included and divided into two groups according to a 75 g oral glucose tolerance test (OGTT): the abnormal glucose metabolism (AGM, n = 257, 57.1%) group and the normal glucose tolerance (NGT, n = 193, 42.9%) group. Indicators of oxidative stress (superoxide dismutase (SOD) and glutathione reductase (GR)) and inflammatory indices (tumor necrosis factor α (TNFα) and interleukin-6 (IL-6)) were all determined by ELISA. LTL and mtDNAcn were measured using a real-time PCR assay. Linear regressions were used to adjust for covariates that might affect the relationship between LTL and mtDNAcn. Mediation analyses were utilized to evaluate the mediators. In the AGM, LTL was correlated with mtDNAcn (r = 0.214, p = 0.001), but no correlation was found in the NGT. The association between LTL and mtDNAcn was weakened after adjusting for inflammatory factors in the AGM (p = 0.087). LTL and mtDNAcn were both inversely related to HbA1c, IL-6, TNFα, and SOD activity. Mediation analysis demonstrated that TNFα was a significant mediator in the telomere-mitochondrial interactome in the AGM. This result suggests that inflammation and oxidative stress may play a vital role in telomere shortening as well as mitochondrial dysfunction. In the subjects with hyperglycemia, a significant positive correlation is observed between LTL and mtDNAcn, which is probably mediated by TNFα. TNFα may be considered a potential therapeutic target against aging-related disease in hyperglycemia.
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Factors Associated with Higher Pro-Inflammatory Tumor Necrosis Factor-α Levels in Young Women with Type 1 Diabetes.
Danielson, KK, Monson, RS, LeCaire, TJ
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2016;(3):140-7
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Abstract
AIMS: While cytokines play a role in the etiology of type 1 diabetes, cytokines later in the disease are less understood. We therefore investigated associations of pro-inflammatory tumor necrosis factor-α levels measured at prolonged disease duration with C-peptide at diagnosis, long-term glycemic control, diabetes duration, clinical factors, and health behaviors. METHODS Data and blood were collected during an ancillary study to the longitudinal Wisconsin Diabetes Registry, a population-based cohort followed since diagnosis of type 1 diabetes. The ancillary study was conducted at 13-18 years diabetes duration, and enrolled premenopausal women age 18-45 years (n=87). RESULTS Higher tumor necrosis factor-α levels at 13-18 years diabetes duration were independently associated with longer duration (p=0.0004) and worse current renal function (p=0.02). Additionally, diabetes duration modified both of the positive associations of tumor necrosis factor-α levels (both interactions p≤0.01) with mean glycemic control during the previous 10 years (significant only in women with longer durations) and current daily caffeine intake (significant only in women with shorter durations). In women with C-peptide measured at diagnosis (n=50), higher tumor necrosis factor-α levels at 13-18 years duration were associated with lower C-peptide (p=0.01), independent of glycemic control during the previous 10 years. CONCLUSIONS Lower residual C-peptide at diagnosis and poor long-term glycemic control independently predicted higher pro-inflammatory tumor necrosis factor-α levels years later. The novel relationship with C-peptide needs confirmation in a larger cohort. Given the association between tumor necrosis factor-α and diabetes complications, further longitudinal studies may help clarify the potentially complex associations between glycemic control, inflammatory cytokines, and complications.
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LC-MS metabolomics of psoriasis patients reveals disease severity-dependent increases in circulating amino acids that are ameliorated by anti-TNFα treatment.
Kamleh, MA, Snowden, SG, Grapov, D, Blackburn, GJ, Watson, DG, Xu, N, Ståhle, M, Wheelock, CE
Journal of proteome research. 2015;(1):557-66
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Psoriasis is an immune-mediated highly heterogeneous skin disease in which genetic as well as environmental factors play important roles. In spite of the local manifestations of the disease, psoriasis may progress to affect organs deeper than the skin. These effects are documented by epidemiological studies, but they are not yet mechanistically understood. In order to provide insight into the systemic effects of psoriasis, we performed a nontargeted high-resolution LC-MS metabolomics analysis to measure plasma metabolites from individuals with mild or severe psoriasis as well as healthy controls. Additionally, the effects of the anti-TNFα drug Etanercept on metabolic profiles were investigated in patients with severe psoriasis. Our analyses identified significant psoriasis-associated perturbations in three metabolic pathways: (1) arginine and proline, (2) glycine, serine and threonine, and (3) alanine, aspartate, and glutamate. Etanercept treatment reversed the majority of psoriasis-associated trends in circulating metabolites, shifting the metabolic phenotypes of severe psoriasis toward that of healthy controls. Circulating metabolite levels pre- and post-Etanercept treatment correlated with psoriasis area and severity index (PASI) clinical scoring (R(2) = 0.80; p < 0.0001). Although the responsible mechanism(s) are unclear, these results suggest that psoriasis severity-associated metabolic perturbations may stem from increased demand for collagen synthesis and keratinocyte hyperproliferation or potentially the incidence of cachexia. Data suggest that levels of circulating amino acids are useful for monitoring both the severity of disease as well as therapeutic response to anti-TNFα treatment.
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Plasma TNF-α and Soluble TNF Receptor Levels after Doxorubicin with or without Co-Administration of Mesna-A Randomized, Cross-Over Clinical Study.
Hayslip, J, Dressler, EV, Weiss, H, Taylor, TJ, Chambers, M, Noel, T, Miriyala, S, Keeney, JT, Ren, X, Sultana, R, et al
PloS one. 2015;(4):e0124988
Abstract
PURPOSE Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines. METHODS Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast cancer. Mesna (360 mg/m2) or saline administration occurred 15 minutes prior and three hours post doxorubicin. Pre-treatment and post-treatment measurements of oxidative stress, TNF-α and related cytokines were evaluated during the two experimental cycles of chemotherapy. RESULTS Co-administration of mesna with chemotherapy reduced post-treatment levels of TNF-related cytokines and TNF-receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2) (p = 0.05 and p = 0.002, respectively). Patients with the highest pre-treatment levels of each cytokine and its receptors were the most likely to benefit from mesna co-administration. CONCLUSIONS The extracellular anti-oxidant mesna, when co-administered during a single cycle of doxorubicin, reduced levels of TNF-α and its receptors after that cycle of therapy, demonstrating for the first time a clinical interaction between mesna and doxorubicin, drugs often coincidentally co-administered in multi-agent regimens. These findings support further investigation to determine whether rationally-timed mesna co-administration with redox active chemotherapy may prevent or reduce the cascade of events that lead to CICI. TRIAL REGISTRATION clinicaltrials.gov NCT01205503.
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Comparison of essential fatty acid intakes and serum levels of inflammatory factors between asthmatic and healthy adults: a case- control study.
Haidari, F, Mohammadshahi, M, Borsi, SH, Haghighizadeh, MH, Malgard, S
Iranian journal of allergy, asthma, and immunology. 2014;(5):335-42
Abstract
Dietary fatty acids play a critical role in modulation of airway inflammation in asthma. This study was conducted to compare dietary intakes of essential fatty acids and serum levels of inflammatory factors in asthmatic and healthy adults, and to examine the potential relationship between inflammatory markers and dietary fatty acids. In this case-control study, 47 asthmatic patients (26 males and 21 females) were compared with 47 controls (24 males and 23 females). Blood samples were taken from case and control groups and tumor necrosis factor-α (TNF-α), high sensitive C-reactive protein (hs-CRP), leptin and adiponectin were determined. Dietary intakes were assessed by semi-quantitative food frequency questionnaire (FFQ). Dietary intakes of omega-3 fatty acids were significantly lower in asthmatic patients compared to controls (p<0.05). Serum concentrations of TNF-α, hs-CRP and leptin were significantly higher in asthmatic patients. There was a significant negative relationship between adiponectin levels and saturated fatty acid intakes in both groups, but the relationship between adiponectin and mono-unsaturated fatty acid intakes was positive and significant only in asthmatic group. No significant correlation between other inflammatory factors and dietary intakes was found in this study. Higher intake of omega-3 and lower levels of inflammatory factors in the healthy control group compared to asthmatic group may explain the protective role of essential fatty acids in asthma. Further studies with larger sample size are needed in this regard.
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Effects of golimumab, an anti-tumour necrosis factor-α human monoclonal antibody, on lipids and markers of inflammation.
Kirkham, BW, Wasko, MC, Hsia, EC, Fleischmann, RM, Genovese, MC, Matteson, EL, Liu, H, Rahman, MU
Annals of the rheumatic diseases. 2014;(1):161-9
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OBJECTIVES To assess the effect of golimumab, with or without methotrexate (MTX), on serum lipids and inflammatory markers of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) in two phase 3, randomised, placebo-controlled trials (GO-BEFORE and GO-FORWARD). METHODS Patients in GO-BEFORE (n=637, MTX-naïve) and GO-FORWARD (n=444, MTX-inadequate response) were randomised to placebo+MTX, golimumab 100 mg+placebo, golimumab 50 mg+MTX, or golimumab 100 mg+MTX. Subcutaneous injections (placebo and golimumab) were given every 4 weeks. Patients with an insufficient response entered early escape at week 16 (GO-FORWARD) or 28 (GO-BEFORE). All placebo+MTX patients in GO-FORWARD crossed over to golimumab 50 mg+MTX at week 24. Changes from baseline to weeks 14 (GO-FORWARD) or 24 (GO-BEFORE), and 52 in serum lipid levels and inflammatory markers were assessed. RESULTS At week 14 in the GO-FORWARD trial, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) increased in golimumab+MTX patients versus MTX-only patients (16.00 vs 2.00 (p<0.001); 3.00 vs 0.00 (p<0.05); 8.00 vs 4.00 (p<0.001); respectively); favourable changes in LDL subfractions were only observed in golimumab-treated patients. At week 24 in GO-BEFORE, TC and LDL increased, and LDL subfractions improved in the MTX-only and golimumab+MTX groups. Inflammatory markers of CVD risk improved significantly with golimumab+MTX versus placebo+MTX in both studies and were generally maintained through week 52. Atherogenic indices were generally stable. CONCLUSIONS While TC and LDL levels increased mildly in RA patients receiving golimumab+MTX, atherogenic indices generally remained stable, favourable changes in LDL subfractions were observed, and inflammatory markers improved.
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Tumor necrosis factor-alpha -308 G>A polymorphism, adherence to Mediterranean diet, and risk of overweight/obesity in young women.
Barchitta, M, Quattrocchi, A, Adornetto, V, Marchese, AE, Agodi, A
BioMed research international. 2014;:742620
Abstract
The present study was conducted in order to (i) characterize the adherence to the Mediterranean diet (MD) pattern and fatty acids (FAs) intakes and (ii) explore interactions between TNFA -308 G>A polymorphism and adherence to MD and FAs intakes, respectively, on overweight/obesity risk. From 2010 to 2013, 380 healthy women were enrolled, and MD score (MDS) and FAs intakes were evaluated by a Food Frequencies Questionnaire in relation to nutritional status. TNFA -308 G/A polymorphism was characterized using PCR-RFLP. A total of 32.6% of women were overweight or obese. Lower mean MDS values were more observed in the younger age group than in the older age group (3.60 versus 4.45). The risk of being overweight/obese was 3.5-fold increased due to poor adherence to MD and was about twofold increased in less educated women. Furthermore, younger age was associated with poor adherence to MD. No evidence for an independent effect of the polymorphism on overweight/obesity risk was found. There was no evidence of biological interaction from the gene-diet interaction analyses. Young women, less educated and with poor adherence to MD, are a target group for the nutritional interventions that aimed to control the obesity risk, thus improving the adherence to MD and particularly the intake of unsaturated FAs.
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Effect of Active Hexose Correlated Compound (AHCC) in alcohol-induced liver enzyme elevation.
Kim, H, Kim, JH, Im, JA
Journal of nutritional science and vitaminology. 2014;(5):348-56
Abstract
To investigate the effects of Active Hexose Correlated Compound (AHCC) supplementation and the mechanism action of AHCC in patients with alcohol-induced mildly elevated liver enzyme levels, participants were randomly allocated to the placebo, 1 g AHCC, or 3 g AHCC group and took the supplement for 12 wk. Subjects visited the hospital for clinical and biochemical measurements, for examination of adverse events, to return unused supplements, and to obtain their next supplements. Biochemical tests including liver enzymes, a questionnaire survey, and anthropometric measurements were collected at baseline and every 4 wk thereafter. Adherence and adverse events were evaluated. After 12 wk of supplementation, the percentage change in alanine aminotransferase (ALT) level was significantly different between the placebo (4.02±59.07%) and both AHCC groups (1 g AHCC 223.89±20.59%, 3 g AHCC 224.09±30.73%) (p=0.04). Serum levels of tumor necrosis factor-α (p<0.05) and interleukin-1β (p<0.01) were significantly lower, while those of adiponectin were higher in both AHCC groups than in the placebo group (p<0.01). AHCC supplementation for 12 wk may improve the levels of liver enzymes and circulating pro-inflammatory and anti-inflammatory cytokines in patients with alcohol-induced liver enzyme elevation with mildly elevated liver enzyme levels.
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Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease.
Loza, MJ, Watt, R, Baribaud, F, Barnathan, ES, Rennard, SI
Respiratory research. 2012;(1):12
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers. Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial. This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation. METHODS Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab. Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109). Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay. RESULTS Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins. This profile was largely independent of smoking status, age, and clinical phenotype. The majority of these associations of serum analytes with COPD are novel findings. Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement. Infliximab did not affect this systemic inflammatory profile. CONCLUSIONS A robust systemic inflammatory profile was associated with COPD. This profile was generally independent of disease severity. Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.