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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 -
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 -
Microbial Drug Resistance (Larchmont,... Oct 2020The present systematic review and meta-analysis study aimed to investigate the prevalence of class 1 integrons and their associated antibiotic resistance in... (Meta-Analysis)
Meta-Analysis
The present systematic review and meta-analysis study aimed to investigate the prevalence of class 1 integrons and their associated antibiotic resistance in uropathogenic A systematic search was conducted to identify studies meeting our inclusion criteria in the Web of Science, PubMed, Embase, Scopus, and Google Scholar electronic databases to the end of July 2019. Finally, 35 articles were selected for data extraction, and meta-analysis was performed using the metaprop program in the STATA, version 11.0, software. The pooled prevalence of class 1 integrons was 47% (95% confidence interval [CI]: 40-54), ranging from 6% to 90%. There was significant heterogeneity among the 35 studies (χ = 840.37; < 0.001; = 95.95%). The results of the subgroup analysis based on characterization of patients indicated that pooled prevalence of class 1 integrons was 52% (95% CI: 41-63; = 14 studies) and 43% (95% CI: 34-54; = 19 studies) in hospitalized and community patients, respectively. The lowest and highest prevalence of antibiotic resistance was observed for imipenem and ampicillin, respectively. According to the results of Begg's and Egger's tests, we did not find significant publication bias both in the included studies and in the subgroup analysis. The results show the high prevalence of class 1 integrons and high level of antibiotic resistance in association with those among uropathogenic . Moreover, the prevalence of class 1 integrons in Asian countries, as well as hospital-acquired urinary tract infection (UTI), was higher than in other countries and community-acquired UTI.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Escherichia coli Infections; Humans; Integrons; Prevalence; Urinary Tract Infections; Uropathogenic Escherichia coli
PubMed: 32282274
DOI: 10.1089/mdr.2019.0467 -
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 -
Molecular Oral Microbiology Aug 2022The objective of this review was to assess the prevalence of antibiotic resistance genes in the oral cavity and identify mobile genetic elements (MGEs) important in... (Review)
Review
The objective of this review was to assess the prevalence of antibiotic resistance genes in the oral cavity and identify mobile genetic elements (MGEs) important in disseminating them. Additionally, to assess if age, geographic location, oral site, bacterial strains and oral disease influence the prevalence of these genes. Three electronic databases (Medline, Embase and the Cochrane Library) were used to search the literature. Journals and the grey literature were also hand searched. English language studies from January 2000 to November 2020 were selected. Primary screening was performed on the titles and abstracts of 1509 articles generated. One hundred and forty-seven full texts were obtained to conduct the second screening with strict inclusion and exclusion criteria. Forty-four final articles agreed with the inclusion criteria. Half of the studies were classed as low quality. tet(M) was the most prevalent gene overall and the conjugative transposon Tn916 the most common MGE associated with antibiotic resistance genes in the oral cavity. In babies delivered vaginally, tet(M) was more prevalent, whilst tet(Q) was more prevalent in those delivered by C-section. Generally, countries with higher consumption of antibiotics had higher numbers of antibiotic resistance genes. Agricultural as well as medical use of antibiotics in a country should always be considered. Between healthy, periodontitis and peri-implantitis subjects, there was no difference in the prevalence of tet(M); however, erm(B), tet(M) and tet(O) were higher in carious active children than the non-carious group. Subjects with poor oral hygiene have more pathogenic bacteria that carry resistance genes compared to those with good oral hygiene. Enterococcus faecalis isolates demonstrated significant tetracycline resistance (tet(M) up to 60% prevalence in samples) and erythromycin resistance (erm(B) up to 61.9% prevalence in samples), periodontal pathogens showed significant beta-lactam resistance with blaZ and cfxA present in up to 90%-97% of samples and the normal oral flora had a high level of erythromycin resistance with mef(A/E) present in 65% of Streptococcus salivarius isolates. The most common resistance gene was tet(M) in root canals, cfxA in subgingival plaque, erm(B) in supragingival plaque and tet(W) in 100% of whole saliva samples. The review highlights that although many studies in this area have been performed, 50% were classed as low quality. We advise the following recommendations to allow firm conclusions to be drawn from future work: the use of large sample sizes, investigate a broad range of antibiotic resistance genes, improved methodologies and reporting to improve the quality of genetic testing in microbiology and randomisation of subject selection.
Topics: Anti-Bacterial Agents; Bacteria; Child; Drug Resistance, Bacterial; Erythromycin; Humans; Interspersed Repetitive Sequences; Microbial Sensitivity Tests; Mouth; Prevalence
PubMed: 35674142
DOI: 10.1111/omi.12375 -
Applied and Environmental Microbiology Feb 2023Site-specific recombinases (integrases) can mediate the horizontal transfer of genomic islands. The ability to integrate large DNA sequences into target sites is very...
Site-specific recombinases (integrases) can mediate the horizontal transfer of genomic islands. The ability to integrate large DNA sequences into target sites is very important for genetic engineering in prokaryotic and eukaryotic cells. Here, we characterized an unprecedented catalogue of 530 tyrosine-type integrases by examining genes potentially encoding tyrosine integrases in bacterial genomic islands. The phylogeny of putative tyrosine integrases revealed that these integrases form an evolutionary clade that is distinct from those already known and are affiliated with novel integrase groups. We systematically searched for candidate integrase genes, and their integration activities were validated in a bacterial model. We verified the integration functions of six representative novel integrases by using a two-plasmid integration system consisting of a donor plasmid carrying the integrase gene and site and a recipient plasmid harboring an site in -deficient Escherichia coli. Further quantitative reverse transcription-PCR (qRT-PCR) assays validated that the six selected integrases can be expressed with their native promoters in E. coli. The region reductions showed that the extent of sites of integrases is approximately 200 bp for integration capacity. In addition, mutational analysis showed that the conserved tyrosine at the C terminus is essential for catalysis, confirming that these candidate proteins belong to the tyrosine-type recombinase superfamily, i.e., tyrosine integrases. This study revealed that the novel integrases from bacterial genomic islands have site-specific recombination functions, which is of physiological significance for their genomic islands in bacterial chromosomes. More importantly, our discovery expands the toolbox for genetic engineering, especially for efficient integration activity. Site-specific recombinases or integrases have high specificity for DNA large fragment integration, which is urgently needed for gene editing. However, known integrases are not sufficient for meeting multiple integrations. In this work, we discovered an array of integrases through bioinformatics analysis in bacterial genomes. Phylogeny and functional assays revealed that these new integrases belong to tyrosine-type integrases and have the ability to conduct site-specific recombination. Moreover, region extent and catalysis site analysis were characterized. Our study provides the methodology for discovery of novel integrases and increases the capacity of weapon pool for genetic engineering in bacteria.
Topics: Integrases; Genomic Islands; Escherichia coli; Tyrosine; Plasmids; Bacteriophages; Attachment Sites, Microbiological
PubMed: 36719242
DOI: 10.1128/aem.01738-22 -
International Journal of Molecular... Jan 2022Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that have become fixed in the human genome. While HERV genes are typically silenced...
Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that have become fixed in the human genome. While HERV genes are typically silenced in healthy somatic cells, there are numerous reports of HERV transcription and translation across a wide spectrum of cancers, while T and B cell responses against HERV proteins have been detected in cancer patients. This review systematically categorizes the published evidence on the expression of and adaptive immune response against specific HERVs in distinct cancer types. A systematic literature search was performed using Medical Search Headings (MeSH) in the PubMed/Medline database. Papers were included if they described the translational activity of HERVs. We present multiple tables that pair the protein expression of specific HERVs and cancer types with information on the quality of the evidence. We find that HERV-K is the most investigated HERV. HERV-W (syncytin-1) is the second-most investigated, while other HERVs have received less attention. From a therapeutic perspective, HERV-K and HERV-E are the only HERVs with experimental demonstration of effective targeted therapies, but unspecific approaches using antiviral and demethylating agents in combination with chemo- and immunotherapies have also been investigated.
Topics: Animals; Antibody Formation; Endogenous Retroviruses; Host-Pathogen Interactions; Humans; Neoplasms; Retroviridae Infections; Viral Proteins
PubMed: 35163254
DOI: 10.3390/ijms23031330 -
The Journal of Surgical Research Aug 2019Human endogenous retroviruses (HERVs) are genetic elements in the human genome, which resulted from ancient retroviral germline infections. HERVs have strong...
BACKGROUND
Human endogenous retroviruses (HERVs) are genetic elements in the human genome, which resulted from ancient retroviral germline infections. HERVs have strong transcriptional promoters and enhancers that affect a cell's transcriptome. They also encode proteins that can exert effects in human cells. This review examines how our increased understanding of HERVs have led to their potential use as biomarkers and immunologic targets.
MATERIAL AND METHODS
PubMed/Medline, Embase, Web of Science, and Cochrane databases were used in a systematic search to identify all articles studying the potential impact of HERVs on surgical diseases. The search included studies that involved clinical patient samples in diseases including cancer, inflammatory conditions, and autoimmune disease. Articles focused on conditions not routinely managed by surgeons were excluded.
RESULTS
Eighty six articles met inclusion and quality criteria for this review and were included. Breast cancer and melanoma have robust evidence regarding the use of HERVs as potential tumor markers and immunologic targets. Reported evidence of the activity of HERVs in colorectal cancer, pancreatic cancer, hepatocellular cancer, prostate and ovarian cancer, germ cell tumors as well as idiopathic pulmonary hypertension, and the inflammatory response in burns was also reviewed.
CONCLUSIONS
Increasingly convincing evidence indicates that HERVs may play a role in solid organ malignancy and present important biomarkers or immunologic targets in multiple cancers. Innovative investigation of HERVs is a valuable focus of translational research and can deepen our understanding of cellular physiology and the effects of endogenous retroviruses on human biology. As strategies for treatment continue to focus on genome-based interventions, understanding the impact of endogenous retroviruses on human disease will be critical.
Topics: Antineoplastic Agents, Immunological; Biomarkers, Tumor; Endogenous Retroviruses; Gene Expression Regulation, Neoplastic; Genome, Human; Humans; Neoplasms; Transcriptome; Translational Research, Biomedical
PubMed: 30933828
DOI: 10.1016/j.jss.2019.02.009 -
Clinical Therapeutics Apr 2019Studies to determine epigenetic changes associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain scarce; however, current evidence clearly...
PURPOSE
Studies to determine epigenetic changes associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain scarce; however, current evidence clearly shows that methylation patterns of genomic DNA and noncoding RNA profiles of immune cells differ between patients and healthy subjects, suggesting an active role of these epigenetic mechanisms in the disease. The present study compares and contrasts the available ME/CFS epigenetic data in an effort to evidence overlapping pathways capable of explaining at least some of the dysfunctional immune parameters linked to this disease.
METHODS
A systematic search of the literature evaluating the ME/CFS epigenome landscape was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Differential DNA methylation and noncoding RNA differential expression patterns associated with ME/CFS were used to screen for the presence of transposable elements using the Dfam browser, a search program nurtured with the Repbase repetitive sequence database and the RepeatMasker annotation tool.
FINDINGS
Unexpectedly, particular associations of transposable elements and ME/CFS epigenetic hallmarks were uncovered. A model for the disease emerged involving transcriptional induction of endogenous dormant transposons and structured cellular RNA interactions, triggering the activation of the innate immune system without a concomitant active infection.
IMPLICATIONS
Repetitive sequence filters (ie, RepeatMasker) should be avoided when analyzing transcriptomic data to assess the potential participation of repetitive sequences ("junk repetitive DNA"), representing >45% of the human genome, in the onset and evolution of ME/CFS. In addition, transposable element screenings aimed at designing cost-effective, focused empirical assays that can confirm or disprove the suspected involvement of transposon transcriptional activation in this disease, following the pilot strategy presented here, will require databases gathering large ME/CFS epigenetic datasets.
Topics: DNA Methylation; DNA Transposable Elements; Epigenesis, Genetic; Epigenomics; Fatigue Syndrome, Chronic; Humans
PubMed: 30910331
DOI: 10.1016/j.clinthera.2019.02.012