Vitamin D affects both innate and adaptive immunity. Most of the effects of vitamin D on innate immunity are anti-inflammatory. In monocytes/macrophages, vitamin D suppresses the production of the ...inflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IL-8. Therefore, the aim of our study was to investigate the relationship between 25(OH)D concentration and selected cytokines-IL-6, TNF-α, and IL-1β, which are hemogram parameters for professional football players. We enrolled 41 Polish premier league soccer players. The mean age, career duration, and VO
were, respectively: 22.7 ± 5.3 years, 14.7 ± 4.5 years, and 55.8 ± 4.0 mL/kg/min. Serum levels of 25(OH)D were measured by electrochemiluminescence (ECLIA) using the Elecsys system (Roche, Switzerland). Serum levels of IL-6, IL-1β, and TNF-α were measured by ELISA (R&D Systems, Minneapolis). Blood count with smear was measured on a Sysmex XT-4000i analyzer (Sysmex Corporation, Japan). Our study showed decreased serum 25(OH)D levels in 78% of the professional players. We found a significant negative correlation between 25(OH)D levels and TNF-α and LYMPH (%). The results also demonstrated a statistically significant positive correlation between vitamin D levels and NEUTH (%), NEUTH (tys/µL), and EOS (tys/µL). Based on the results of our study, we concluded that football players from Poland are not protected against vitamin D insufficiency in winter months. Moreover, vitamin D deficiency may be associated with an increased pro-inflammatory risk in well-trained athletes.
Alterations in circulating Cu and Zn are negative predictors of survival in neoplastic patients and are known during lung cancer. However, no data on predicting mortality of lung cancer patients ...based on the level of these elements in the blood have been presented to date. The aims of this prospective cohort study were as follows: (i) To evaluate the disturbances in serum and whole blood Cu and Zn, (ii) to assess the relationships between serum and whole blood Cu and Zn status and clinical, sociodemographic, and nutritional data, and (iii) to investigate the association of Cu and Zn status with all-cause mortality in lung cancer. Naïve-treatment lung cancer patients (
= 167) were characterized in terms of sociodemographic, clinical, and anthropometric data and dietary intake and compared with sex-matched control subjects (
= 48). Whole blood and serum Cu and Zn status was determined by atomic absorption spectrometry. Cox proportional hazards models adjusted for multiple confounders/mediators were used to estimate the association between all-cause death and Cu and Zn status. Sex, cardiovascular disease, chronic obstructive pulmonary disease, clinical stage, and hemoglobin, platelet, and glucose concentrations significantly differentiated Cu and Zn status. All-cause mortality in lung cancer patients was positively associated with serum Cu levels, Cu:Zn ratio, and whole blood Zn levels. However, an advanced clinical stage of disease was the strongest predictor of all-cause mortality. Circulatory status of Cu and Zn might be included in routine clinical characteristics of patients with lung cancer patients as additional prognostic variables, but only after further more detail studies.
Lung cancer is responsible for the most cancer-related mortality worldwide and the mechanism of its development is poorly understood. Proteomics has become a powerful tool offering vital knowledge ...related to cancer development. Using a two-dimensional difference gel electrophoresis (2D-DIGE) approach, we sought to compare tissue samples from non-small-cell lung cancer (NSCLC) patients taken from the tumor center and tumor margin. Two subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were compared. Data are available via ProteomeXchange with identifier PXD032736 and PXD032962 for ADC and SCC, respectively. For ADC proteins, 26 significant canonical pathways were identified, including Rho signaling pathways, a semaphorin neuronal repulsive signaling pathway, and epithelial adherens junction signaling. For SCC proteins, nine significant canonical pathways were identified, including hypoxia-inducible factor-1α signaling, thyroid hormone biosynthesis, and phagosome maturation. Proteins differentiating the tumor center and tumor margin were linked to cancer invasion and progression, including cell migration, adhesion and invasion, cytoskeletal structure, protein folding, anaerobic metabolism, tumor angiogenesis, EMC transition, epithelial adherens junctions, and inflammatory responses. In conclusion, we identified several proteins that are important for the better characterization of tumor development and molecular specificity of both lung cancer subtypes. We also identified proteins that may be important as biomarkers and/or targets for anticancer therapy.
A comparative analysis of blood samples (depleted of albumin and IgG) obtained from lung cancer patients before chemotherapy versus after a second cycle of chemotherapy was performed using ...two-dimensional difference gel electrophoresis (2D-DIGE). The control group consisted of eight patients with non-cancerous lung diseases, and the experimental group consisted of four adenocarcinoma (ADC) and four squamous cell carcinoma (SCC) patients. Analyses of gels revealed significant changes in proteins and/or their proteoforms between control patients and lung cancer patients, both before and after a second cycle of chemotherapy. Most of these proteins were related to inflammation, including acute phase proteins (APPs) such as forms of haptoglobin and transferrin, complement component C3, and clusterin. The variable expression of APPs can potentially be used for profiling lung cancer. The greatest changes observed after chemotherapy were in transferrin and serotransferrin, which likely reflect disturbances in iron turnover after chemotherapy-induced anaemia. Significant changes in plasma proteins between ADC and SCC patients were also revealed, suggesting use of plasma vitronectin as a potential marker of SCC.
•There are no differences in vitamin D metabolites and ratios between inactive men and athletes who train indoors and outdoors.•Regular long-term physical activity has no effect on resting ...concentrations of vitamin D metabolites.•Free vitamin D does not correlate stronger with vitamin D metabolites and VMRs compared to total.
Higher levels of physical activity are related to higher 25-(OH)D levels. Total 25-(OH)D (25-(OH)DT) are routinely used in clinical practice to assess vitamin D, however novel biomarkers are currently being investigated as free 25-(OH)D (25-(OH)DF) or vitamin D metabolite ratios (VMRs). The primary aim of our study was to assess 25-(OH)DF, vitamin D metabolites and VMRs in inactive men and athletes. A secondary aim was to check whether regular physical activity influence on vitamin D metabolome. A tertiary aim was to determine the relationship between 25-(OH)DT, 25-(OH)DF, vitamin D binding protein (VDBP), vitamin D metabolites and VMRs in this cohort.
A total of 69 participants (27 inactive men, 18 indoor and 24 outdoor athletes) participated in the study. Vitamin D metabolites (25-(OH)DT, 24,25-(OH)2D3, 3-epi-25-(OH)D3, and 1,25-(OH)2D) were assessed using LC-MS/MS. The 25-(OH)DF concentration was calculated based on serum albumin and VDBP levels.
There were no differences in vitamin D metabolites and VMRs between inactive men and between the two groups of athletes. We showed a strong relationship between 25-(OH)DT, 25-(OH)DF and 24,25-(OH)D3, 3-epi-25(OH)D3, 24,25-(OH)2D3:25-(OH)D3 VMR in each group. Analysis showed that 25-(OH)DT, 25-(OH)DF inversely associated with 25-(OH)D3:24,25-(OH)2D3, 25-(OH)D3:3-epi-25-(OH)D3, 1,25-(OH)2D:24,25-(OH)2D3 ratios in inactive men and athletes (indoor and outdoor).
On the basis of our results, we concluded that regular long-term physical activity has no effect on the concentration of vitamin D metabolites at rest. Furthermore, free vitamin D does not correlate more strongly with vitamin D metabolites and VMRs compared to total.
Silicon in nutritional amounts provides benefits for bone health and cognitive function. The relationship between silicon intake from a common daily diet and silicon blood level has been scarcely ...elucidated, so far. The aim of this study was to analyze the associations between plasma silicon levels and the total and bioavailable silicon intake-along with the contribution of silicon made by food groups-in a healthy adult Polish population. Si intake was evaluated in 185 healthy adults (94 females and 91 males, aged 20-70) using a 3-day dietary recall and a database on the silicon content in foods, which was based on both previously published data and our own research. Fasting plasma silicon levels were measured in 126 consenting subjects, using graphite furnace atomic absorption spectrometry. The silicon intake in the Polish population differed significantly according to sex, amounting to 24.0 mg/day in women and 27.7 mg/day in men. The median plasma silicon level was 152.3 µg/L having no gender dependency but with a negative correlation with age. Significant correlations were found between plasma silicon level and total and bioavailable silicon intake, as well as water intake in the diet (
= 0.18,
= 0.044;
= 0.23,
= 0.011;
= 0.28,
= 0.002, respectively). Silicon intakes from non-alcoholic beverages, cereal foods, and carotene-rich vegetables were also positively associated with plasma silicon levels. These results may help establish dietary silicon recommendations and formulate practical advice on dietary choices to ensure an appropriate supply of silicon. The outcome of this study, however, needs to be confirmed by large-scale epidemiological investigations.
Altered systemic redox status is often observed in lung cancer. However, detailed information on factors other, than smoking, which influence this perturbation is rather scarce. Elevated oxidative ...stress has been linked with disturbances in glucose metabolism before, but such associations have not been investigated in lung cancer. The aim of this study was to evaluate the relationship between systemic parameters of glucose metabolism and redox status in lung cancer patients (LC). Biochemical variables related to circulating glucose, i.e. glucose, insulin, c-peptide, fructosamine (FA), and glucose metabolism, i.e. β-hydroxybutyrate (BHB), lactate (LACT), non-esterified fatty acids (NEFAs), as well as redox status i.e. total antioxidant status (TAS) and total oxidant status (TOS) were determined for LC (n = 122) and control subjects (CS) (n = 84). HOMA-IR and the oxidative stress index (OSI) were calculated. LC patients had an altered redox status and glucose metabolism compared to CS. Positive correlations in LC were observed between TOS, OSI and circulating glucose as well as FA, while TAS positively correlated with BHB and NEFAs. In contrast, in metastatic LC, NEFAs and BHB positively correlated with OSI. Smoking status additionally stratified the observed relationships. In conclusion, we found that parameters related to circulating glucose or non-enzymatic glycation were correlated with oxidative stress (TOS and OSI), while metabolites such as BHB and NEFAs were correlated with antioxidant capacity (TAS). Metastasis prevalence and smoking seem to influence these correlations. However, the detailed mechanism of this relationship requires further research, in particular as regards the surprising positive correlation between NEFAs and TAS.
Objective
Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify ...the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.
Methods
In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open‐label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure.
Results
In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty‐seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment RCT: 364 days (95% confidence interval CI = 223–535) vs 124 days (95% CI = 33–149); OLT: 426 days (95% CI = 258–628) vs 106 days (95% CI = 11–149). At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio OR = 0.21, p = 0.032), drug‐resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted.
Interpretation
Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2021;89:304–314
Epigenetics can contribute to lipid disorders in obesity. The DNA methylation pattern can be the cause or consequence of high blood lipids. The aim of the study was to investigate the DNA methylation ...profile in peripheral leukocytes associated with elevated LDL-cholesterol level in overweight and obese individuals.
To identify the differentially methylated genes, genome-wide DNA methylation microarray analysis was performed in leukocytes of obese individuals with high LDL-cholesterol (LDL-CH, ≥ 3.4 mmol/L) versus control obese individuals with LDL-CH, < 3.4 mmol/L. Biochemical tests such as serum glucose, total cholesterol, HDL cholesterol, triglycerides, insulin, leptin, adiponectin, FGF19, FGF21, GIP and total plasma fatty acids content have been determined. Oral glucose and lipid tolerance tests were also performed. Human DNA Methylation Microarray (from Agilent Technologies) containing 27,627 probes for CpG islands was used for screening of DNA methylation status in 10 selected samples. Unpaired t-test and Mann-Whitney U-test were used for biochemical and anthropometric parameters statistics. For microarrays analysis, fold of change was calculated comparing hypercholesterolemic vs control group. The q-value threshold was calculated using moderated Student's t-test followed by Benjamini-Hochberg multiple test correction FDR.
In this preliminary study we identified 190 lipid related CpG loci differentially methylated in hypercholesterolemic versus control individuals. Analysis of DNA methylation profiles revealed several loci engaged in plasma lipoprotein formation and metabolism, cholesterol efflux and reverse transport, triglycerides degradation and fatty acids transport and β-oxidation. Hypermethylation of CpG loci located in promoters of genes regulating cholesterol metabolism: PCSK9, LRP1, ABCG1, ANGPTL4, SREBF1 and NR1H2 in hypercholesterolemic patients has been found. Novel epigenetically regulated CpG sites include ABCG4, ANGPTL4, AP2A2, AP2M1, AP2S1, CLTC, FGF19, FGF1R, HDLBP, LIPA, LMF1, LRP5, LSR, NR1H2 and ZDHHC8 genes.
Our results indicate that obese individuals with hypercholesterolemia present specific DNA methylation profile in genes related to lipids transport and metabolism. Detailed knowledge of epigenetic regulation of genes, important for lipid disorders in obesity, underlies the possibility to influence target genes by changing diet and lifestyle, as DNA methylation is reversible and depends on environmental factors. These findings give rise for further studies on factors that targets methylation of revealed genes.
Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in ...obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25-40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT β = 0.16 (confidence interval (CI): 0.01-0.32), triglycerides β = 0.21 (95% CI: 0.06-0.36, and FGF-21 β = 0.20 (95%CI: 0.03-0.37); and postprandial GIP with GGT β = 0.17 (95%CI: 0.03-0.32). The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02-5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut-liver cross-talk.
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