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Journal of Neurology Aug 2018Although existing studies show that reactivation of the human endogenous retrovirus (HERVs) plays a leading role in multiple sclerosis (MS) progression, the... (Review)
Review
BACKGROUND
Although existing studies show that reactivation of the human endogenous retrovirus (HERVs) plays a leading role in multiple sclerosis (MS) progression, the practitioners are yet to establish effective approaches for managing MS without jeopardizing the patients' immune systems.
AIM
To provide up-to-date knowledge on the specific roles played by the reactivation of the HERVs in the pathogenesis of MS.
MATERIALS AND METHODS
A systematic review of 70 peer-reviewed journals accessed via PubMed was conducted. The searches generated more than 600 sources that were evaluated based on three step in and exclusion criteria. The selected sources were critically analyzed vis-à-vis the paper's hypothesis which posits that the HERVs reactivation does not directly cause the MS, but triggers a demyelination process by promoting the pathogenic effects of the retroviruses. The paper further documents the advancements in the therapeutic applications resulting from the immunohistological analysis and pathological studies aimed at minimizing the adverse consequences of the HERVs reactivation.
RESULTS AND DISCUSSIONS
Only three out of the 70 reviewed sources did not find provide evidence linking the reactivation of HERV and MS progression. On the other hand, overwhelming pieces of evidence confirm that the reactivations often drive the demyelinating plaques by initiating microglial inflammation. Pathological examinations reveal that the inflammatory monocytes (Ly6ChiCCR2 + CX3CR1lo) trigger the reactivation of the malignant T cells that are responsible for the progression of MS. These findings are promoting new discoveries as far as managing MS is concerned.
Topics: Endogenous Retroviruses; Humans; Multiple Sclerosis; Retroviridae Infections
PubMed: 29423611
DOI: 10.1007/s00415-018-8783-1 -
PloS One 2017The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS.
OBJECTIVE
To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients.
METHODS
Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association.
RESULTS
43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W (MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF.
CONCLUSIONS
This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS.
Topics: Endogenous Retroviruses; Humans; Multiple Sclerosis
PubMed: 28207850
DOI: 10.1371/journal.pone.0172415 -
International Journal of Cardiology Jun 2016Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in processes underlying cardiovascular... (Review)
Review
BACKGROUND
Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in processes underlying cardiovascular disease (CVD), including atherosclerosis, inflammation, hypertension and diabetes.
METHODS
Eleven databases were searched for studies investigating the association between epigenetic marks (either global, site-specific or genome-wide methylation of DNA and histone modifications) and CVD.
RESULTS
Of the 3459 searched references, 31 studies met our inclusion criteria (26 cross-sectional studies and 5 prospective studies). Overall, 12,648 individuals were included, with total of 4037 CVD events. The global DNA methylation assessed at long-interspersed nuclear element (LINE-1) was inversely associated with CVD, independent of established cardiovascular risk factors. Conversely, a higher degree of global DNA methylation measured at Alu repeats or by the LUMA method was associated with the presence of CVD. The studies reported epigenetic regulation of 34 metabolic genes (involved in fetal growth, glucose and lipid metabolism, inflammation, atherosclerosis and oxidative stress) in blood cells to be related with CVD. Among them, 5 loci were validated and methylation at F2RL3 was reported in two large prospective studies to predict cardiovascular disease beyond the traditional risk factors.
CONCLUSIONS
Current evidence supports an association between genomic DNA methylation and CVD. However, this review highlights important gaps in the existing evidences including lack of large-scale epigenetic investigations, needed to reliably identify genomic loci where DNA methylation is related to risk of CVD.
Topics: Alu Elements; Cardiovascular Diseases; DNA Methylation; Epigenesis, Genetic; Female; Genetic Loci; Genetic Predisposition to Disease; Histones; Humans; Male
PubMed: 27038728
DOI: 10.1016/j.ijcard.2016.03.062 -
BMJ Open Jan 2015To systematically review the evidence for the impact of study design and setting on the interpretation of tuberculosis (TB) transmission using clustering derived from... (Review)
Review
Effect of study design and setting on tuberculosis clustering estimates using Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR): a systematic review.
OBJECTIVES
To systematically review the evidence for the impact of study design and setting on the interpretation of tuberculosis (TB) transmission using clustering derived from Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) strain typing.
DATA SOURCES
MEDLINE, EMBASE, CINHAL, Web of Science and Scopus were searched for articles published before 21st October 2014.
REVIEW METHODS
Studies in humans that reported the proportion of clustering of TB isolates by MIRU-VNTR were included in the analysis. Univariable meta-regression analyses were conducted to assess the influence of study design and setting on the proportion of clustering.
RESULTS
The search identified 27 eligible articles reporting clustering between 0% and 63%. The number of MIRU-VNTR loci typed, requiring consent to type patient isolates (as a proxy for sampling fraction), the TB incidence and the maximum cluster size explained 14%, 14%, 27% and 48% of between-study variation, respectively, and had a significant association with the proportion of clustering.
CONCLUSIONS
Although MIRU-VNTR typing is being adopted worldwide there is a paucity of data on how study design and setting may influence estimates of clustering. We have highlighted study design variables for consideration in the design and interpretation of future studies.
Topics: Bacterial Typing Techniques; Cluster Analysis; Humans; Interspersed Repetitive Sequences; Minisatellite Repeats; Molecular Epidemiology; Mycobacterium tuberculosis; Polymorphism, Restriction Fragment Length; Reproducibility of Results; Research Design; Tuberculosis
PubMed: 25609667
DOI: 10.1136/bmjopen-2014-005636 -
Prostate Cancer and Prostatic Diseases Mar 2015The role of global DNA methylation in prostate cancer (PCa) remains largely unknown. Our aim was to summarize evidence on the role of global DNA hypomethylation in PCa... (Review)
Review
BACKGROUND
The role of global DNA methylation in prostate cancer (PCa) remains largely unknown. Our aim was to summarize evidence on the role of global DNA hypomethylation in PCa development and progression.
METHODS
We searched PubMed through December 2013 for all studies containing information on global methylation levels in PCa tissue and at least one non-tumor comparison tissue and/or studies reporting association between global methylation levels in PCa tissue and survival, disease recurrence or at least one clinicopathological prognostic factor. We summarized results using non-parametric comparisons and P-value summary methods.
RESULTS
We included 15 studies in the review: 6 studies with both diagnostic and prognostic information, 5 studies with only diagnostic information and 4 studies with only prognostic information. Quantitative meta-analysis was not possible because of the large heterogeneity in molecular techniques, types of tissues analyzed, aims and study designs. Summary statistical tests showed association of DNA hypomethylation with PCa diagnosis (P<0.006) and prognosis (P<0.001). Restriction to studies assessing 5-methylcytosine or long interspersed nucleotide element-1 revealed results in the same direction. Analyses restricted to specific clinicopathological features showed association with the presence of metastasis and tumor stage in all tests with P<0.03, and no association with Gleason score (all tests P>0.1 except for the weighted Z-test, P=0.05).
CONCLUSION
DNA hypomethylation was associated with PCa development and progression. However, due to the heterogeneity and small sample sizes of the included studies, along with the possibility of publication bias, this association requires additional assessment.
Topics: DNA Methylation; Disease Progression; Humans; Long Interspersed Nucleotide Elements; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Prognosis; Prostatic Neoplasms; PubMed
PubMed: 25384337
DOI: 10.1038/pcan.2014.45 -
PloS One 2014A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk.
METHODS
A systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used.
RESULTS
A total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: -6.40, 95% CI: -7.71, -5.09; p<0.001). The significant difference in methylation levels was confirmed in tissue samples (MD -7.55; 95% CI: -9.14, -65.95; p<0.001), but not in blood samples (MD: -0.26, 95% CI: -0.69, 0.17; p = 0.23). LINE-1 methylation levels were significantly lower in colorectal and gastric cancer patients than in controls (MD: -8.33; 95% CI: -10.56, -6.10; p<0.001 and MD: -5.75; 95% CI: -7.75, -3.74; p<0.001) whereas, no significant difference was observed for hepatocellular cancer.
CONCLUSIONS
The present meta-analysis adds new evidence to the growing literature on the role of LINE-1 hypomethylation in human cancer and demonstrates that LINE-1 methylation levels were significantly lower in cancer patients than in control samples, especially in certain cancer types. This result was confirmed in tissue samples, both fresh/frozen or FFPE specimens, but not in blood. Further studies are needed to better clarify the role of LINE-1 methylation in specific subgroups, considering both cancer and sample type, and the methods of measurement.
Topics: Biomarkers, Tumor; DNA Methylation; Epigenesis, Genetic; Humans; Long Interspersed Nucleotide Elements; Neoplasms; Risk
PubMed: 25275447
DOI: 10.1371/journal.pone.0109478