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Public Health Genomics 2017The goal of this systematic review and meta-analysis is to determine the effect of diet on telomere length. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The goal of this systematic review and meta-analysis is to determine the effect of diet on telomere length.
METHODS
We searched the following databases: MEDLINE, Embase, LILACS, CINAHL, ISI Web of Science, and Scopus, as well as the Cochrane Central Register of Controlled Trials and the National Institutes of Health, from inception to December 2016. Articles that assessed effects of diet on telomere length were included.
RESULTS
A total of 2,128 studies were identified, 30 were read in full, and 7 were systematically reviewed. Five RCTs were included in the meta-analysis, covering 9 diets; a total of 533 participants were included. Study heterogeneity (I2) was 89%, and differences were not identified regarding average telomere lengths (mean difference 1.06; 95% CI -1.53 to 3.65).
CONCLUSION
The available evidence suggests that there is no effect of diet on telomere length, but the strong heterogeneity in the type and duration of dietary interventions does not allow any final statement on the absence of an effect of diet on telomere length.
Topics: Aged; Diet; Female; Humans; Life Expectancy; Male; Middle Aged; Statistics as Topic; Telomere; Telomere Shortening
PubMed: 29439273
DOI: 10.1159/000486586 -
Microbiology and Molecular Biology... Mar 2018The use of lentiviral vectors for therapeutic purposes has shown promising results in clinical trials. The ability to produce a clinical-grade vector at high yields... (Review)
Review
The use of lentiviral vectors for therapeutic purposes has shown promising results in clinical trials. The ability to produce a clinical-grade vector at high yields remains a critical issue. One possible obstacle could be cellular factors known to inhibit human immunodeficiency virus (HIV). To date, five HIV restriction factors have been identified, although it is likely that more factors are involved in the complex HIV-cell interaction. Inhibitory factors that have an adverse effect but do not abolish virus production are much less well described. Therefore, a gap exists in the knowledge of inhibitory factors acting late in the HIV life cycle (from transcription to infection of a new cell), which are relevant to the lentiviral vector production process. The objective was to review the HIV literature to identify cellular factors previously implicated as inhibitors of the late stages of lentivirus production. A search for publications was conducted on MEDLINE via the PubMed interface, using the keyword sequence "HIV restriction factor" or "HIV restriction" or "inhibit HIV" or "repress HIV" or "restrict HIV" or "suppress HIV" or "block HIV," with a publication date up to 31 December 2016. Cited papers from the identified records were investigated, and additional database searches were performed. A total of 260 candidate inhibitory factors were identified. These factors have been identified in the literature as having a negative impact on HIV replication. This study identified hundreds of candidate inhibitory factors for which the impact of modulating their expression in lentiviral vector production could be beneficial.
Topics: Clinical Trials as Topic; DNA Replication; Gene Expression Regulation; Gene Transfer Techniques; Genetic Vectors; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Immunity, Cellular; Lentivirus; Virus Replication
PubMed: 29321222
DOI: 10.1128/MMBR.00051-17 -
International Journal of Molecular... Dec 2017Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of... (Review)
Review
Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of lethality with increased age. Biological aging results in progressive attrition of telomeres, which are the repetitive DNA sequences at the end of chromosomes. These telomeres play an important role in protection of genomic DNA from end-to-end fusions. Telomere maintenance and telomere attrition-associated senescence of endothelial and smooth muscle cells have been indicated to be part of the pathogenesis of degenerative vascular diseases. This systematic review provides an overview of telomeres, telomere-associated proteins and telomerase to the formation and progression of aneurysms of the thoracic ascending aorta. A better understanding of telomere regulation in the vascular pathology might provide new therapeutic approaches. Measurements of telomere length and telomerase activity could be potential prognostic biomarkers for increased risk of death in elderly patients suffering from an aortic aneurysm.
Topics: Aging; Animals; Aortic Aneurysm, Thoracic; Biomarkers; DNA; Humans; Mice; Rats; Risk Factors; Telomerase; Telomere; Telomere Shortening
PubMed: 29267201
DOI: 10.3390/ijms19010003 -
Diabetologia Feb 2018Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA... (Review)
Review
DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA levels: a systematic review and replication in a case-control sample of the Lifelines study.
AIMS/HYPOTHESIS
Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA levels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study.
METHODS
We performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results. For replication purposes we selected 100 unique CpGs identified in peripheral blood, pancreas, adipose tissue and liver from 15 EWASs, using study-specific Bonferroni-corrected significance thresholds. Methylation data (Illumina 450K array) in whole blood from 100 type 2 diabetic individuals and 100 control individuals from the Lifelines study were available. Multivariate linear models were used to examine the associations of the specific CpGs with type 2 diabetes and glycaemic traits.
RESULTS
From the 52 CpGs identified in blood and selected for replication, 15 CpGs showed nominally significant associations with type 2 diabetes in the Lifelines sample (p < 0.05). The results for five CpGs (in ABCG1, LOXL2, TXNIP, SLC1A5 and SREBF1) remained significant after a stringent multiple-testing correction (changes in methylation from -3% up to 3.6%, p < 0.0009). All associations were directionally consistent with the original EWAS results. None of the selected CpGs from the tissue-specific EWASs were replicated in our methylation data from whole blood. We were also unable to replicate any of the CpGs associated with HbA levels in the healthy control individuals of our sample, while two CpGs (in ABCG1 and CCDC57) for fasting glucose were replicated at a nominal significance level (p < 0.05).
CONCLUSIONS/INTERPRETATION
A number of differentially methylated CpGs reported to be associated with type 2 diabetes in the EWAS literature were replicated in blood and show promise for clinical use as disease biomarkers. However, more prospective studies are needed to support the robustness of these findings.
Topics: Blood Glucose; CpG Islands; DNA Methylation; Diabetes Mellitus, Type 2; Epigenesis, Genetic; Fasting; Genome-Wide Association Study; Glycated Hemoglobin; Humans
PubMed: 29164275
DOI: 10.1007/s00125-017-4497-7 -
Nutricion Hospitalaria Oct 2017Few studies have evaluated the relationship between diet quality and telomere integrity in humans. Telomeres are regions of non-coding DNA localized at the end of each... (Review)
Review
BACKGROUND
Few studies have evaluated the relationship between diet quality and telomere integrity in humans. Telomeres are regions of non-coding DNA localized at the end of each chromosome whose length, in addition to indicating life expectancy, indicates an overall health status. The objective of this systematic review is to compile the existing evidence on the relationship between telomere length and diet quality to further explore the impact that some nutrients, foods and dietary patterns may have on telomere homeostasis and therefore, in precision nutrition strategies.
MATERIAL AND METHODS
A bibliographic review was performed in the PubMed database to identify published articles (in English or Spanish) until December 2016 that met the following criteria: included human subjects; cross-sectional studies; case-control studies; prospective cohort studies or intervention studies; evaluating the relationship of nutrients, foods or dietary patterns on telomere integrity. The search strategy included the following keywords: nutrients or food OR food groups OR diet OR dietary pattern OR eating pattern OR dietary habits OR diet type AND telomere attrition OR telomere length. In total, 19 cross-sectional studies, five case-control studies, five prospective cohort studies, and two intervention studies were included, including those articles that were found for being listed in other publications.
RESULTS
Positive associations were found between telomere length and adherence to the Mediterranean diet and consumption of vegetables and fruits. The results observed for other nutrients, foods or dietary patterns were incoherent although it seems that processed meats, cereals, alcohol and sweetened beverages could be associated with shorter telomeres.
CONCLUSIONS
Dietary intervention, and in particular the promotion of a Mediterranean-style diet, may play a role in the protection of telomere integrity.
Topics: Diet; Diet, Mediterranean; Health Status; Humans; Telomere; Telomere Shortening
PubMed: 29130723
DOI: 10.20960/nh.1181 -
Oncotarget Sep 2017Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA... (Review)
Review
BACKGROUND
Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality. Furthermore the replication-dependent activity of PARP inhibitor helps to maintain the differential effect between tumoral and healthy tissues. Inhibition of chromatin remodeling, G2/M arrest, vasodilatory effect induced by PARP inhibitor, also participate to their radio-sensitization effect.
MATERIALS AND METHODS
Here, after highlighting mechanisms of PARP inhibitors radiosensitization we methodically searched PubMed, Google Scholar, Cochrane Databases and meeting proceedings for human pre-clinical and clinical studies that evaluated PARP inhibitor radiosensitizing effect. Enhancement ratio, when available, was systematically reported.
RESULTS
Sixty four studies finally met our selection criteria and were included in the analysis. Only three pre-clinical studies didn't find any radiosensitizing effect. Median enhancement ratio vary from 1,3 for prostate tumors to 1,5 for lung cancers. Nine phase I or II trials assessed safety data.
CONCLUSION
PARP inhibitors are promising radiosensitizers, but need more clinical investigation. The next ten years will be determining for judging their real potential.
PubMed: 28978184
DOI: 10.18632/oncotarget.19079 -
Environmental Research Oct 2017Cigarette smoking is a risk factor for ageing-related disease, but its association with biological ageing, indicated by telomere length, is unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cigarette smoking is a risk factor for ageing-related disease, but its association with biological ageing, indicated by telomere length, is unclear.
METHODS
We systematically reviewed evidence evaluating association between smoking status and telomere length. Searches were performed in MEDLINE (Ovid) and EMBASE (Ovid) databases, combining variation of keywords "smoking" and "telomere". Data was extracted for study characteristics and estimates for association between smoking and telomere length. Quality of studies was assessed with a risk of bias score, and publication bias was assessed with a funnel plot. I test was used to observe heterogeneity. Meta-analysis was carried out to compare mean difference in telomere length by smoking status, and a dose-response approach was carried out for pack-years of smoking and telomere length. A sensitivity analysis was carried out to examine sources of heterogeneity.
RESULTS
A total of 84 studies were included in the review, and 30 among them were included in our meta-analysis. Potential bias was addressed in half of included studies, and there was little evidence of small study bias. Telomere length was shorter among ever smokers compared to never smokers (summary standard mean difference [SMD]: -0.11 (95% CI -0.16 to -0.07)). Similarly, shorter telomere length was found among smokers compared to non-smokers, and among current smokers compared to never or former smokers. Dose-response meta-analysis suggested an inverse trend between pack-years of smoking and telomere length. However, heterogeneity among some analyses was observed.
CONCLUSION
Shorter telomeres among ever smokers compared to those who never smoked may imply mechanisms linking tobacco smoke exposure to ageing-related disease.
Topics: Humans; Risk Factors; Smoking; Telomere Homeostasis; Telomere Shortening; Tobacco Smoke Pollution
PubMed: 28704792
DOI: 10.1016/j.envres.2017.06.038 -
Gastroenterology Research and Practice 2016The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical... (Review)
Review
The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical trials were searched in PUBMED, MEDLINE, EMBASE, and CNKI databases up to February 15, 2016. Nine trials including 764 patients met the entry criteria. In direct meta-analysis, TDF showed a stronger antiviral effect than any one of ETV, LAM/ADV, and ADV against LAM-R hepatitis B virus. LAM/ADV therapy was superior to ADV in suppressing viral replication. ETV achieved similar rate of HBV DNA undetectable compared to ADV or LAM/ADV. In network meta-analysis, TDF had higher rates of HBV DNA undetectable compared to ETV (OR, 24.69; 95% CrI: 5.36-113.66), ADV (OR, 37.28; 95% CrI: 9.73-142.92), or LAM/ADV (OR, 21.05; 95% CrI: 5.70-77.80). However, among ETV, ADV, and LAM/ADV, no drug was clearly superior to others in HBV DNA undetectable rate. Moreover, no significant difference in the rate of ALT normalization or HBeAg loss was observed compared the four rescue strategies with each other. TDF appears to be a more effective rescue therapy than LAM/ADV, ETV, or ADV. LAM plus ADV therapy was a better treatment option than ETV or ADV alone for patients with LAM-R.
PubMed: 27672391
DOI: 10.1155/2016/3435965 -
Medicine Apr 2016Iron is required for most forms of organisms, and it is the most essential element for the functions of many iron-containing proteins involved in oxygen transport,... (Review)
Review
Iron is required for most forms of organisms, and it is the most essential element for the functions of many iron-containing proteins involved in oxygen transport, cellular respiration, DNA replication, and so on. Disorders of iron metabolism are associated with diverse diseases, including anemias (e.g., iron-deficiency anemia and anemia of chronic diseases) and iron overload diseases, such as hereditary hemochromatosis and β-thalassemia. Hepcidin (encoded by Hamp gene) is a peptide hormone synthesized by hepatocytes, and it plays an important role in regulating the systematic iron homeostasis. As the systemic iron regulator, hepcidin, not only controls dietary iron absorption and iron egress out of iron storage cells, but also induces iron redistribution in various organs. Deregulated hepcidin is often seen in a variety of iron-related diseases including anemias and iron overload disorders. In the case of iron overload disorders (e.g., hereditary hemochromatosis and β-thalassemia), hepatic hepcidin concentration is significantly reduced.Since hepcidin deregulation is responsible for iron disorder-associated diseases, the purpose of this review is to summarize the recent findings on therapeutics targeting hepcidin.Continuous efforts have been made to search for hepcidin mimics and chemical compounds that could be used to increase hepcidin level. Here, a literature search was conducted in PubMed, and research papers relevant to hepcidin regulation or hepcidin-centered therapeutic work were reviewed. On the basis of literature search, we recapitulated recent findings on therapeutic studies targeting hepcidin, including agonists and antagonists to modulate hepcidin expression or its downstream signaling. We also discussed the molecular mechanisms by which hepcidin level and iron metabolism are modulated.Elevating hepcidin concentration is an optimal strategy to ameliorate iron overload diseases, and also to relieve β-thalassemia phenotypes by improving ineffective erythropoiesis. Relative to the current conventional therapies, such as phlebotomy and blood transfusion, therapeutics targeting hepcidin would open a new avenue for treatment of iron-related diseases.
Topics: Hepcidins; Homeostasis; Humans; Iron; Iron Metabolism Disorders
PubMed: 27057839
DOI: 10.1097/MD.0000000000003150 -
Brain, Behavior, and Immunity May 2016Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes.
OBJECTIVE
We conducted a systematic review and meta-analysis to determine the association between self-reported, perceived psychological stress (PS) and telomere length (TL).
DATA SOURCES
We searched 3 databases (PubMed, PsycInfo, and Scopus), completed manual searches of published and unpublished studies, and contacted all study authors to obtain potentially relevant data.
STUDY SELECTION
Two independent reviewers assessed studies for original research measuring (but not necessarily reporting the correlation between) PS and TL in human subjects. 23 studies met inclusion criteria; 22 (totaling 8948 subjects) could be meta-analyzed.
DATA EXTRACTION AND SYNTHESIS
We assessed study quality using modified MINORS criteria. Since not all included studies reported PS-TL correlations, we obtained them via direct calculation from author-provided data (7 studies), contact with authors (14 studies), or extraction from the published article (1 study).
MAIN OUTCOMES AND MEASURES
We conducted random-effects meta-analysis on our primary outcome, the age-adjusted PS-TL correlation. We investigated potential confounders and moderators (sex, life stress exposure, and PS measure validation) via post hoc subset analyses and meta-regression.
RESULTS
Increased PS was associated with a very small decrease in TL (n=8724 total; r=-0.06; 95% CI: -0.10, -0.008; p=0.01; α=0.025), adjusting for age. This relationship was similar between sexes and within studies using validated measures of PS, and marginally (nonsignificantly) stronger among samples recruited for stress exposure (r=-0.13; vs. general samples: b=-0.11; 95% CI: -0.27, 0.01; p=0.05; α=0.013). Publication bias may exist; correcting for its effects attenuated the relationship.
CONCLUSIONS AND RELEVANCE
Our analysis finds a very small, statistically significant relationship between increased PS (as measured over the past month) and decreased TL that may reflect publication bias, although fully parsing the effects of publication bias from other sample-size correlates is challenging, as discussed. The association may be stronger with known major stressors and is similar in magnitude to that noted between obesity and TL. All included studies used single measures of short-term stress; the literature suggests long-term chronic stress may have a larger cumulative effect. Future research should assess for potential confounders and use longitudinal, multidimensional models of stress.
Topics: Animals; Humans; Publication Bias; Statistics as Topic; Stress, Psychological; Telomere; Telomere Shortening
PubMed: 26853993
DOI: 10.1016/j.bbi.2016.02.002