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Sustaining efficient immune functions with regular physical exercise in the COVID-19 era and beyond.
Furtado, GE, Letieri, RV, Caldo-Silva, A, Sardão, VA, Teixeira, AM, de Barros, MP, Vieira, RP, Bachi, ALL
European journal of clinical investigation. 2021;(5):e13485
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Abstract
The new coronavirus (SARS-CoV-2) appearance in Wuhan, China, did rise the new virus disease (COVID-19), which spread globally in a short time, leading the World Health Organization to declare a new global pandemic. To contain and mitigate the spread of SARS-CoV-2, specific public health procedures were implemented in virtually all countries, with a significant impact on society, making it difficult to keep the regular practice of physical activity. It is widely accepted that an active lifestyle contributes to the improvement of general health and preservation of cardiovascular, respiratory, osteo-muscular and immune system capacities. The positive effects of regular physical activity on the immune system have emerged as a pivotal trigger of general health, underlying the beneficial effects of physical activity on multiple physiological systems. Accordingly, recent studies have already pointed out the negative impact of physical inactivity caused by the social isolation imposed by the public sanitary authorities due to COVID-19. Nevertheless, there are still no current narrative reviews evaluating the real impact of COVID-19 on active lifestyle or even discussing the possible beneficial effects of exercise-promoted immune upgrade against the severity or progression of COVID-19. Based on the consensus in the scientific literature, in this review, we discuss how an exercise adherence could adequately improve immune responses in times of the 'COVID-19 Era and beyond'.
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A Comprehensive, Multidisciplinary, Personalized, Lifestyle Intervention Program Is Associated with Increased Leukocyte Telomere Length in Children and Adolescents with Overweight and Obesity.
Paltoglou, G, Raftopoulou, C, Nicolaides, NC, Genitsaridi, SM, Karampatsou, SI, Papadopoulou, M, Kassari, P, Charmandari, E
Nutrients. 2021;(8)
Abstract
Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life.
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Exposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocytes.
Bozack, AK, Boileau, P, Wei, L, Hubbard, AE, Sillé, FCM, Ferreccio, C, Acevedo, J, Hou, L, Ilievski, V, Steinmaus, CM, et al
Environmental health : a global access science source. 2021;(1):79
Abstract
BACKGROUND Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS. METHODS DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs. RESULTS In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR < 0.05). Using meta-analyzed results, we identified 11 DMRs and 11 DVRs in PBMC samples, and 16 DMRs and 19 DVRs in PBMC and buccal cell samples. One region annotated to LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate. CONCLUSIONS Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.
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Selenocompounds and Sepsis: Redox Bypass Hypothesis for Early Diagnosis and Treatment: Part A-Early Acute Phase of Sepsis: An Extraordinary Redox Situation (Leukocyte/Endothelium Interaction Leading to Endothelial Damage).
Forceville, X, Van Antwerpen, P, Preiser, JC
Antioxidants & redox signaling. 2021;(2):113-138
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Abstract
Significance: Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die. Multiple attempts to control sepsis at an early stage have been unsuccessful. Recent Advances: Major events in early sepsis include activation and binding of leukocytes and endothelial cells in the microcirculation, damage of the endothelial surface layer (ESL), and a decrease in the plasma concentration of the antioxidant enzyme, selenoprotein-P. These events induce an increase in intracellular redox potential and lymphocyte apoptosis, whereas apoptosis is delayed in monocytes and neutrophils. They also induce endothelial mitochondrial and cell damage. Critical Issues: Neutrophil production increases dramatically, and aggressive immature forms are released. Leukocyte cross talk with other leukocytes and with damaged endothelial cells amplifies the inflammatory response. The release of large quantities of reactive oxygen, halogen, and nitrogen species as a result of the leukocyte respiratory burst, endothelial mitochondrial damage, and ischemia/reperfusion processes, along with the marked decrease in selenoprotein-P concentrations, leads to peroxynitrite damage of the ESL, reducing flow and damaging the endothelial barrier. Future Directions: Endothelial barrier damage by activated leukocytes is a time-sensitive event in sepsis, occurring within hours and representing the first step toward organ failure and death. Reducing or stopping this event is necessary before irreversible damage occurs.
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Leukocyte Trafficking via Lymphatic Vessels in Atherosclerosis.
Yeo, KP, Lim, HY, Angeli, V
Cells. 2021;(6)
Abstract
In recent years, lymphatic vessels have received increasing attention and our understanding of their development and functional roles in health and diseases has greatly improved. It has become clear that lymphatic vessels are critically involved in acute and chronic inflammation and its resolution by supporting the transport of immune cells, fluid, and macromolecules. As we will discuss in this review, the involvement of lymphatic vessels has been uncovered in atherosclerosis, a chronic inflammatory disease of medium- and large-sized arteries causing deadly cardiovascular complications worldwide. The progression of atherosclerosis is associated with morphological and functional alterations in lymphatic vessels draining the diseased artery. These defects in the lymphatic vasculature impact the inflammatory response in atherosclerosis by affecting immune cell trafficking, lymphoid neogenesis, and clearance of macromolecules in the arterial wall. Based on these new findings, we propose that targeting lymphatic function could be considered in conjunction with existing drugs as a treatment option for atherosclerosis.
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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids.
Jhun, MA, Mendelson, M, Wilson, R, Gondalia, R, Joehanes, R, Salfati, E, Zhao, X, Braun, KVE, Do, AN, Hedman, ÅK, et al
Nature communications. 2021;(1):3987
Abstract
Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.
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Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial.
Sindi, S, Solomon, A, Kåreholt, I, Hovatta, I, Antikainen, R, Hänninen, T, Levälahti, E, Laatikainen, T, Lehtisalo, J, Lindström, J, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;(3):491-498
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Abstract
BACKGROUND Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). METHODS Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989). RESULTS This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264). CONCLUSIONS This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits. CLINICAL TRIALS REGISTRATION NUMBER NCT01041989.
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The role of phagocytic leukocytes following flexible ureterenoscopy, for the treatment of kidney stones: an observational, clinical pilots-study.
Hughes, SF, Moyes, AJ, Lamb, RM, Ella-Tongwiis, P, Snyper, NYF, Shergill, I
European journal of medical research. 2020;(1):68
Abstract
BACKGROUND The number of patients undergoing flexible ureterenoscopy (FURS) for the treatment of kidney stones (renal calculi) is increasing annually, and as such the development of post-operative complications, such as acute kidney injury (AKI), haematuria and infection is likely to increase. Phagocytic leukocytes are white blood cells that help fight foreign material such as bacteria and viruses, and they are intrinsically involved in the inflammatory reaction. Investigating the role of phagocytic leukocytes following FURS has not been widely researched. The main aim of the study was to evaluate the role phagocytic leukocytes (neutrophils and monocytes) function, in patients undergoing FURS for the treatment of kidney stones (renal calculi). METHODS Fourteen consecutive patients aged between 27 and 70 years (median 49.5 years) undergoing FURS for the treatment of kidney stones were recruited (seven males, seven females). Blood samples were collected from each patient at four time points: baseline (pre-operatively) followed by 30, 120 and 240 min post-operatively. Mononuclear (MN) and polymorphonuclear (PMN) leukocyte sub-populations were isolated by density gradient centrifugation techniques. Neutrophil and monocyte cell function was investigated by measuring the cell surface expression of CD62L (L-selectin), CD11b (Mac-1), CD99 and the intracellular production of hydrogen peroxide (H2O2), via flow cytometry. RESULTS Significant increases was observed in monocyte CD62L expression post FURS for the treatment of kidney stones (p ≤ 0.05); while significant decreases were observed in neutrophil CD62L. The levels of the other activation markers CD11b, CD99 and H2O2 corresponded to the increases and decreases seen in CD62L for monocytes and neutrophils respectively, though the changes were not statistically significant (p > 0.05). Limiting factors for this study were the relatively small sample size, and restriction on the recruitment time points. CONCLUSIONS This study demonstrates that following FURS for the treatment of kidney stones, monocytes are rapidly activated and produce potent reactive oxygen intermediates. Interestingly, the pattern of expression in neutrophils suggests that these cells are deactivated in response to the treatment. The leukocyte biomarkers assessed during this investigation may have a role in monitoring the 'normal' post-operative response, as no complications occurred in any of the patients; or may help predict potential infectious complications (e.g. urosepsis) that can occur during the post-operative period. This data, however, will need to be validated and reproduced in larger multi-centre studies.
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COVID-19 and hydatidiform mole.
Abbas, AM, Ahmed, L, Salem, AS, Elsamman, SH, Refai, A, Fathy, SK, Ahmed, OA, Shalotut, AS, AbdelWahab, RA
American journal of reproductive immunology (New York, N.Y. : 1989). 2020;(5):e13310
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Abstract
The emergence of coronavirus disease 2019 (COVID-19) as a pandemic threatens the entire world resulting in severe consequences for people's health. Pregnant patients with COVID-19 had immune dysregulation that could result in abnormal pregnancy outcomes such as hydatidiform mole (HM), recurrent pregnancy loss, and early-onset preeclampsia. In this article, we tried to summarize the possible association between COVID-19 and the HM's development by reviewing the role of NOD-Like Receptor (NLR) Family Pyrin Domain Containing 7 (NLRP7), cytokines, zinc, and leukocytes in the pathogenesis of HM.
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Laparoscopic sleeve gastrectomy induces molecular changes in peripheral white blood cells.
Beisani, M, Pappa, S, Moreno, P, Martínez, E, Tarascó, J, Granada, ML, Puig, R, Cremades, M, Puig-Domingo, M, Jordà, M, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(2):592-598
Abstract
BACKGROUND & AIMS Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. METHODS From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. RESULTS Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylation/demethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. CONCLUSIONS FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes.