-
1.
Walnut Consumption for Two Years and Leukocyte Telomere Attrition in Mediterranean Elders: Results of a Randomized Controlled Trial.
Freitas-Simoes, TM, Cofán, M, Blasco, MA, Soberón, N, Foronda, M, Serra-Mir, M, Roth, I, Valls-Pedret, C, Doménech, M, Ponferrada-Ariza, E, et al
Nutrients. 2018;(12)
Abstract
Randomized controlled trials on diet and shortening of leukocyte telomere length (LTL) mostly focus on marine-derived n-3 polyunsaturated fatty acids (PUFA). Walnuts are a sustainable source of n-3 PUFA. We investigated whether inclusion of walnuts (15% of energy) in the diet for 2 years would maintain LTL in cognitively healthy elders (63⁻79 years old) compared to a control group (habitual diet, abstaining from walnuts). This opportunistic sub-study was conducted within the Walnuts and Healthy Aging study, a dual-centre (Barcelona, Spain and Loma Linda University, California) parallel trial. A sub-set of the Barcelona site participants were randomly assigned to the walnut (n = 80) or control group (n = 69). We assessed LTL at baseline and at 2 years and we conducted repeated-measures ANCOVA with 2 factors: time (baseline, 2 years) and group (control, walnut) and their interaction. Adjusted means (95% confidence interval) of LTL (in kb) in controls were 7.360 (7.084,7.636) at baseline and 7.061 (6.835,7.288) after 2 years; corresponding values in the walnut group were 7.064 (6.807,7.320) and 7.074 (6.864,7.284). The time × intervention interaction was nearly significant (p = 0.079), suggestive of a trend of walnut consumption in preserving LTL. This exploratory research finding should be confirmed in trials with adequate statistical power.
-
2.
Characterization in humans of in vitro leucocyte maximal telomerase activity capacity and association with stress.
de Punder, K, Heim, C, Przesdzing, I, Wadhwa, PD, Entringer, S
Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2018;(1741)
-
-
Free full text
-
Abstract
The goal of this study was to develop and validate a measure of maximal telomerase activity capacity (mTAC) for use in human studies of telomere biology, and to determine its association with measures of stress and stress responsivity. The study was conducted in a population of 28 healthy young women and men who were assessed serially across two separate days, at multiple time points, and in response to a standardized laboratory stressor. Venous blood was collected at each of these multiple assessments, and an in vitro mitogen challenge (phytohaemagglutinin supplemented with interleukin-2) was used to stimulate telomerase activity in leucocytes. After first establishing the optimal post-stimulation time course to characterize mTAC, we determined the within-subject stability and the between-subject variability of mTAC. The major findings of our study are as follows: (i) the optimal time point to quantify human leucocyte mTAC appears to be at 72 h after mitogen stimulation; (ii) mTAC exhibits substantial within-subject stability (correlations were in the range of r 0.68-0.82) and between-subject variability, with a high intra-class coefficient (0.70), indicating greater between-subject relative to within-subject variability; (iii) mTAC is not influenced by situational factors including time of day, cortisol, acute stress exposure and immune cell distribution in the pre-stimulation blood sample; and (iv) a significant proportion of the between-subject variability in mTAC is associated with measures of stress and stress responsivity (mTAC is lower in subjects reporting higher levels of perceived (chronic) stress and exhibiting higher psychophysiological stress reactivity). Based collectively on these findings, it appears that mTAC, as proposed and operationalized, empirically meets the key criteria to represent a potentially useful individual difference measure of telomerase activity capacity of human leucocytes.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.
-
3.
Membrane lipid environment: Potential modulation of chemokine receptor function.
Thelen, M, Legler, DF
Cytokine. 2018;:72-75
Abstract
Migration of leukocytes is typically mediated by G protein-coupled receptors (GPCRs) upon activation by specific ligands that range from small peptides, chemokines to a variety of lipidic molecules. The heptahelical receptors are highly dynamic structures and the signaling efficiency largely depends on the discrete contact with the ligand. In addition, several allosteric modulators of receptor activity have been reported, which do not induce migration by themselves. Another important mechanism modulating the activity of GPCRs is their local environment. Not only the membrane lipid composition influences the activity, but also direct binding of lipids, in particular cholesterol, was shown to alter receptor signaling properties. Recent findings indicate that also chemokine receptor activity is modulated by membrane lipids. In this short review we discuss this new paradigm and potential consequences for chemokine-induced migration.
-
4.
Leukocyte telomere length in paediatric critical illness: effect of early parenteral nutrition.
Verstraete, S, Vanhorebeek, I, van Puffelen, E, Derese, I, Ingels, C, Verbruggen, SC, Wouters, PJ, Joosten, KF, Hanot, J, Guerra, GG, et al
Critical care (London, England). 2018;(1):38
Abstract
BACKGROUND Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. METHODS Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. RESULTS Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P < 0.0001)). Adjusted for potential baseline determinants and leukocyte composition, early PN was associated with telomere shortening during PICU stay as compared with late PN (estimate early versus late PN -0.021 T/S-units, 95% CI -0.038; 0.004, P = 0.01). Other independent determinants of telomere length identified in this model were age, gender, baseline telomere length and fraction of neutrophils in the sample from which the DNA was extracted. Telomere shortening with early PN was independent of post-randomisation factors affected by early PN, including longer length of PICU stay, larger amounts of insulin and higher risk of infection. CONCLUSIONS Shorter than normal leukocyte telomeres are present in critically ill children admitted to the PICU. Early initiation of PN further shortened telomeres, an effect that was independent of other determinants. Whether such telomere-shortening predisposes to long-term consequences of paediatric critical illness should be further investigated in a prospective follow-up study. TRIAL REGISTRATION ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012.
-
5.
Differential Gene Expression in Peripheral White Blood Cells with Permissive Underfeeding and Standard Feeding in Critically Ill Patients: A Descriptive Sub-study of the PermiT Randomized Controlled Trial.
Arabi, YM, Al-Balwi, M, Hajeer, AH, Jawdat, D, Sadat, M, Al-Dorzi, HM, Tamim, H, Afesh, L, Almashaqbeh, W, Alkadi, H, et al
Scientific reports. 2018;(1):17984
Abstract
The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.
-
6.
Obesity impairs leukocyte-endothelium cell interactions and oxidative stress in humans.
López-Domènech, S, Bañuls, C, Díaz-Morales, N, Escribano-López, I, Morillas, C, Veses, S, Orden, S, Álvarez, Á, Víctor, VM, Hernández-Mijares, A, et al
European journal of clinical investigation. 2018;(8):e12985
Abstract
BACKGROUND To evaluate the relationship between leukocyte-endothelial cell interactions and oxidative stress parameters in non-diabetic patients with different grades of obesity. MATERIAL AND METHODS For this cross-sectional study, 225 subjects were recruited from January 1, 2014 to December 31, 2016 and divided into groups according to BMI (<30 kg/m2 , 30-40 kg/m2 and >40 kg/m²). We determined clinical parameters, systemic inflammatory markers, soluble cellular adhesion molecules, leukocyte-endothelium cell interactions-rolling flux, velocity and adhesion-, oxidative stress parameters-total ROS, total superoxide, glutathione-and mitochondrial membrane potential in leukocytes. RESULTS We verified that HOMA-IR and hsCRP increased progressively as obesity developed, whereas A1c, IL6 and TNFα were augmented in the BMI > 40 kg/m² group. The cellular adhesion molecule sP-selectin was increased in patients with obesity, while sICAM, total ROS, total superoxide and mitochondrial membrane potential were selectively higher in the BMI > 40 kg/m² group. Obesity induced a progressive decrease in rolling velocity and an enhancement of rolling flux and leukocyte adhesion. CONCLUSION Our findings reveal that endothelial dysfunction markers are altered in human obesity and are associated with proinflammatory cytokines and increased oxidative stress parameters.
-
7.
The kinetics of white blood cell and the predictive factors of leukocytosis under oral or intravenous arsenic as the first-line treatment for acute promyelocytic leukemia.
Wang, F, Jia, JS, Wang, J, Zhao, T, Jiang, Q, Jiang, H, Zhu, HH
Leukemia research. 2017;:84-88
Abstract
OBJECTIVE We aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment. METHODS The absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n=35) or ATO (n=29). The end points were the dynamic changes of the WBC counts during induction. The time points started at day 1 and were selected over 3-day intervals for 28days. RESULTS Among the 64 included patients, the median initial and peak WBC counts were 1.78×109/L (range 0.31-9.89) and 12.16×109/L (range 1.56-80.01), respectively. The incidence of differentiation syndrome was 9.38%. The dynamic changes in leukocytosis showed a single peak wave in all the patients, and the median time to peak was 10 (range 2-26) days. A higher WBC count was observed in the RIF group than in the ATO group after 10days of treatment (9.22×109/L vs. 4.10×109/L, p=0.015). Patients with the peak WBC count >10×109/L had a shorter WBC doubling time compared to patients with a lower peak WBC (RIF group 4days vs. 7days, p=0.001; ATO group 4.5days vs. 23days, p=0.002). Univariate and multivariable analyses showed that the doubling time of WBC is an independent factor for the peak WBC count. CONCLUSION Different kinetics of WBC proliferation were observed during induction with oral arsenic plus ATRA and ATO plus ATRA. The doubling time of WBC is an important independent factor for predicting the peak WBC count.
-
8.
Effects of Astaxanthin on Liver and Leukocyte Parameters in Healthy Climacteric Women: Preliminary Data.
Chen, JT, Kotani, K
Journal of medicinal food. 2017;(7):724-725
-
9.
Oxidative stress and DNA damage in the cord blood of preterm infants.
Norishadkam, M, Andishmand, S, Zavar Reza, J, Zare Sakhvidi, MJ, Hachesoo, VR
Mutation research. Genetic toxicology and environmental mutagenesis. 2017;:20-24
Abstract
Preterm birth infants are more susceptible to oxidative stress and aftermaths unwanted outcomes such as DNA damage due to hyperoxic stress. In this study, we compared the DNA strand breaks as one of the results of DNA oxidation in white blood cells, malondialdehyde (oxidative stress marker), catalase and superoxide dismutase activity, and total antioxidant capacity (markers of antioxidant defense) in a cord blood plasma of a group of preterm (n=25) and full term births (n=25). The primary DNA damage and plasma oxidative stress markers were significantly higher in a preterm group (p<0.05). Cord plasma activity of superoxide dismutase was significantly lower in preterm infants (p≤0.001). However, there were no significant differences in the cord blood total antioxidant capacity, catalase activity and malondialdehyde in preterm and term infants. Among the oxidative stress markers, the malondialdehyde concentration showed the strongest effect size (1.54; 95%CI: 0.9-2.17). For comet parameters, the most powerful effect size was observed for tail length (5.24; 95% CI: 4.05-6.42). However, tail DNA percent and tail moment were also significantly higher in cases compared to controls. Significant negative correlation was observed between comet assay parameters and birth weight and gestational age when all cases and controls entered into the analysis. There was no significant association between the levels of oxidative stress markers and early DNA damage in cord blood plasma with future nutritional tolerance in preterm infants. In the present study, the primary DNA damage and plasma oxidative stress markers significantly were increased in a preterm group. Preterm babies are more prone to the outcomes related to the early DNA damage. Tail DNA percent does not depend on experimental conditions as other parameters (tail length and thus also tail moment) and can be used for comparison with other studies.
-
10.
A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss.
Roumans, NJ, Vink, RG, Fazelzadeh, P, van Baak, MA, Mariman, EC
The American journal of clinical nutrition. 2017;(5):1054-1062
-
-
Free full text
-
Abstract
Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain.Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain.Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gene expression changes for a broad set of ECM-related genes were correlated with the weight-regain percentage (WR%).Results: A total of 26 of the 277 genes were significantly correlated with WR% during WL, WS, or the DI periods. Most correlations were observed in the VLCD group during the WS period. Four genes code for leukocyte-specific receptors. These and other genes belong to a group of 26 genes, among which the expression changes were highly correlated (r ≥ 0.7, P ≤ 0.001). This group could be divided into 3 subclusters linking to 2 biological processes-leukocyte integrin gene activity and ECM remodeling-and a link to insulin sensitivity was also apparent.Conclusions: Our present findings indicate the importance of adipose tissue leukocytes for the risk of weight regain. ECM modification also seems to be involved, and we observed a link to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT01559415.