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Placenta Mar 2020Preeclampsia is a medical condition affecting 5-10% of pregnancies. It has serious effects on the health of the pregnant mother and developing fetus. While possible...
Preeclampsia is a medical condition affecting 5-10% of pregnancies. It has serious effects on the health of the pregnant mother and developing fetus. While possible causes of preeclampsia are speculated, there is no consensus on its etiology. The advancement of big data and high-throughput technologies enables to study preeclampsia at the new and systematic level. In this review, we first highlight the recent progress made in the field of preeclampsia research using various omics technology platforms, including epigenetics, genome-wide association studies (GWAS), transcriptomics, proteomics and metabolomics. Next, we integrate the results in individual omic level studies, and show that despite the lack of coherent biomarkers in all omics studies, inhibin is a potential preeclamptic biomarker supported by GWAS, transcriptomics and DNA methylation evidence. Using network analysis on the biomarkers of all the literature reviewed here, we identify four striking sub-networks with clear biological functions supported by previous molecular-biology and clinical observations. In summary, omics integration approach offers the promise to understand molecular mechanisms in preeclampsia.
Topics: Epigenesis, Genetic; Female; Genomics; Humans; Inhibins; Pre-Eclampsia; Pregnancy; Proteome; Transcriptome
PubMed: 32056783
DOI: 10.1016/j.placenta.2020.01.008 -
Gut Aug 2015Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available.
METHODS
We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative).
RESULTS
Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analyses on 156 variants involving 101 genes. We identified 11 variants significantly associated with disease risk and assessed to have a high level of summary evidence: MUC1 rs2070803 at 1q22 (diffuse carcinoma subgroup), MTX1 rs2075570 at 1q22 (diffuse), PSCA rs2294008 at 8q24.2 (non-cardia), PRKAA1 rs13361707 5p13 (non-cardia), PLCE1 rs2274223 10q23 (cardia), TGFBR2 rs3087465 3p22 (Asian), PKLR rs3762272 1q22 (diffuse), PSCA rs2976392 (intestinal), GSTP1 rs1695 11q13 (Asian), CASP8 rs3834129 2q33 (mixed) and TNF rs1799724 6p21.3 (mixed), with the first nine variants characterised by a low FPRP. We also identified polymorphisms with lower quality significant associations (n=110).
CONCLUSIONS
We have identified several high-quality biomarkers of gastric cancer susceptibility. These data will form the backbone of an annually updated online resource that will be integral to the study of gastric carcinoma genetics and may inform future screening programmes.
Topics: Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Neoplasm Proteins; Polymorphism, Genetic; Risk Factors; Stomach Neoplasms
PubMed: 25731870
DOI: 10.1136/gutjnl-2015-309168 -
Biology of Sex Differences May 2018Differences in cardiovascular diseases are evident in men and women throughout life and are mainly attributed to the presence of sex hormones and chromosomes. Epigenetic...
BACKGROUND
Differences in cardiovascular diseases are evident in men and women throughout life and are mainly attributed to the presence of sex hormones and chromosomes. Epigenetic mechanisms drive the regulation of the biological processes that may lead to CVD and are possibly influenced by sex. In order to gain an overview of the status quo on sex differences in cardiovascular epigenetics, we performed a systematic review.
MATERIALS AND METHODS
A systematic search was performed on PubMed and Embase for studies mentioning cardiovascular disease, epigenetics, and anything related to sex differences. The search returned 3071 publications to be screened. Primary included publications focused on cardiovascular and epigenetics research. Subsequently, papers were assessed for including both sexes in their studies and checked for appropriate sex stratification of results.
RESULTS
Two independent screeners identified 75 papers in the proper domains that had included both sexes. Only 17% (13 papers out of 75) of these publications stratified some of their data according to sex. All remaining papers focused on DNA methylation solely as an epigenetic mechanism. Of the excluded papers that included only one sex, 86% (24 out 28) studied males, while 14% (4 out of 28) studied females.
CONCLUSION
Our overview indicates that the majority of studies into cardiovascular epigenetics do not show their data stratified by sex, despite the well-known sex differences in CVD. All included and sex-stratified papers focus on DNA methylation, indicating that a lot of ground is still to gain regarding other epigenetic mechanisms, like chromatin architecture, and histone modifications. More attention to sex in epigenetic studies is warranted as such integration will advance our understanding of cardiovascular disease mechanisms in men and women.
Topics: Cardiovascular Diseases; Epigenesis, Genetic; Female; Humans; Male; Sex Characteristics
PubMed: 29792221
DOI: 10.1186/s13293-018-0180-z -
Life (Basel, Switzerland) Feb 2024Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined... (Review)
Review
Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined with biomechanical and biochemical peculiar conditions within each musculoskeletal district. While the contribution of genetic and epigenetic factors to knee OA is well-recognized, their precise role in disease management remains an area of active research. Such a field is particularly heterogeneous, calling for regular analysis and summarizing of the data that constantly emerge in the scientific literature, often sparse and scant of integration. The aim of this study was to systematically identify and synthesize all new evidence that emerged in human and animal model studies published between 2020 and 2023. This was necessary because, to the best of our knowledge, articles published before 2019 (and partly 2020) had already been included in systematic reviews that allowed to identify the ones concerning the knee joint. The review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only peer-reviewed articles were considered for inclusion. A total of 40 studies were identified, showing promising results in terms either of biomarker identification, new insight in mechanism of action or potential therapeutic targets for knee OA. DNA methylation, histone modification and ncRNA were all mechanisms involved in epigenetic regulation of the knee. Most recent evidence suggests that epigenetics is a most promising field with the long-term goal of improving understanding and management of knee OA, but a variety of research approaches need greater consolidation.
PubMed: 38398778
DOI: 10.3390/life14020269 -
Frontiers in Public Health 2023Cervical cancer (CC) is the fourth most common neoplasia affecting women worldwide. Female sex workers (FSWs) are among those at highest risk of developing and...
BACKGROUND
Cervical cancer (CC) is the fourth most common neoplasia affecting women worldwide. Female sex workers (FSWs) are among those at highest risk of developing and succumbing to CC. Yet, they are often overlooked in CC screening programs and have limited access to CC healthcare globally. The development of CC screening programs for this high-risk target population is necessary to reduce the global burden of this disease and to reach the World Health Organization's objective of accelerating the elimination of CC.
OBJECTIVE
This review summarizes findings on CC screening programs for FSWs that have been implemented worldwide, and assesses their effectiveness and sustainability.
METHODS
A scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A literature search was performed on PubMed, Swisscovery, and Google Scholar for studies describing and assessing CC screening programs for FSWs. In addition, targeted searching online Non-Governmental and International Organizations websites identified grey literature. A single reviewer screened titles and abstracts, and extracted data from the research findings.
RESULTS
The search identified 13 articles published from 1989 to 2021. All implemented programs successfully reached FSWs and provided them with CC screening during the study period. The most effective and sustainable strategies were the Screen and Treat approach, introducing CC screening into existing STI services in drop-in or outreach clinics, HPV-DNA self-sampling, and integrating sex-workers-specific services in public health facilities. Follow-up was deemed the main challenge in providing and enhancing CC healthcare to FSWs with rates of loss to follow-up ranging from 35 to 60%.
CONCLUSION
FSWs are often omitted in national CC screening programs. The further development and improvement of CC healthcare, including follow-up systems, for this high-priority target population are imperative.
Topics: Humans; Female; Early Detection of Cancer; Uterine Cervical Neoplasms; Sex Workers; Ambulatory Care Facilities; Mass Screening
PubMed: 37841741
DOI: 10.3389/fpubh.2023.1226779 -
PeerJ 2022This study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
We enrolled all relevant studies published up to 5 January 2022. Three primary subgroups were investigated: qualitative or quantitative ctDNA analyses, combined alpha-fetoprotein (AFP), and ctDNA assay. In addition to the three primary subgroups, we also evaluated the diagnostic value of methylated SEPTIN9 (mSEPT9), which has been studied extensively in the diagnosis of hepatocellular carcinoma. After a search based on four primary databases, we used a bivariate linear mixed model to analyze the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). We also plotted hierarchical summary receiver operating characteristics (HSROC) and utilized lambda as well as the area under the curve (AUC) to create summary receiver operating characteristic (SROC) curves to estimate the diagnostic value of ctDNA.
RESULTS
A total of 59 qualified articles with 9,766 subjects were incorporated into our meta-analysis. The integrated SEN, SPE, and DOR in the qualitative studies were 0.50 (95% CI [0.43-0.56]), 0.90 (95% CI [0.86-0.93]), and 8.72 (95% CI [6.18-12.32]), respectively, yielding an AUC of 0.78 and lambda of 1.93 (95% CI [1.56-2.33]). For quantitative studies, the corresponding values were 0.69 (95% CI [0.63-0.74]), 0.84 (95% CI [0.77-0.89]), 11.88 (95% CI [7.78-18.12]), 0.81, and 2.32 (95% CI [1.96-2.69]), respectively. Six studies were included to evaluate the SETP9 methylation, which yielded an AUC of 0.86, a SEN of 0.80 (95% CI [0.71-0.87]), and a SPE of 0.77 (95% CI [0.68-0.85]). Likewise, ctDNA concentration yielded an AUC of 0.73, with a SEN of 0.63 (95% CI [0.56-0.70]) and a SPE of 0.86 (95% CI [0.74-0.93]). AFP combined with ctDNA assay resulted in an AUC of 0.89, with a SEN of 0.82 (95% CI [0.77-0.86]) and a SPE of 0.84 (95% CI [0.76-0.90]).
CONCLUSION
This study shows that circulating tumor DNA, particularly mSEPT9, shows promising diagnostic potential in HCC; however, it is not enough to diagnose HCC independently, and ctDNA combined with conventional assays such as AFP can effectively improve diagnostic performance.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Circulating Tumor DNA; ROC Curve
PubMed: 36348665
DOI: 10.7717/peerj.14303 -
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 -
Neural Regeneration Research Dec 2024The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and...
The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies. Despite the need for non-invasively accessible biomarkers, the majority of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers, which require invasive collection procedures. Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers. In the present study, after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease, we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients. A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289 articles. After screening and exclusion, 34 relevant articles were derived for systematic review. Alpha-synuclein, the histopathological hallmark of Parkinson's disease, has been the most investigated Parkinson's disease biomarker in saliva, with oligomeric alpha-synuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls, while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein, and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease. Beyond alpha-synuclein, other biomarkers targeting different molecular pathways have been explored in the saliva of Parkinson's disease patients: total tau, phosphorylated tau, amyloid-β1-42 (pathological protein aggregation biomarkers); DJ-1, heme-oxygenase-1, metabolites (altered energy homeostasis biomarkers); MAPLC-3beta (aberrant proteostasis biomarker); cortisol, tumor necrosis factor-alpha (inflammation biomarkers); DNA methylation, miRNA (DNA/RNA defects biomarkers); acetylcholinesterase activity (synaptic and neuronal network dysfunction biomarkers); Raman spectra, proteome, and caffeine. Despite a few studies investigating biomarkers targeting molecular pathways different from alpha-synuclein in Parkinson's disease, these results should be replicated and observed in studies on larger cohorts, considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes. Although the need for standardization in sample collection and processing, salivary-based biomarkers studies have reported encouraging results, calling for large-scale longitudinal studies and multicentric assessments, given the great molecular potentials and the non-invasive accessibility of saliva.
PubMed: 38595280
DOI: 10.4103/NRR.NRR-D-23-01677 -
Clinical Epigenetics 2016Epigenetic mechanisms are important for the regulation of gene expression and differentiation in the fetus and the newborn child. Symptoms of maternal depression and... (Review)
Review
INTRODUCTION
Epigenetic mechanisms are important for the regulation of gene expression and differentiation in the fetus and the newborn child. Symptoms of maternal depression and antidepressant use affects up to 20 % of pregnant women, and may lead to epigenetic changes with life-long impact on child health. The aim of this review is to investigate whether there is an association between exposure to maternal antidepressants during pregnancy and epigenetic changes in the newborn.
MATERIAL AND METHODS
Systematic literature searches were performed in MEDLINE and EMBASE combining MeSH terms covering epigenetic changes, use of antidepressant medication, pregnancy and newborns. A keyword search was also performed. We included studies on pregnant women and their children where there was a history of maternal depressed mood or anxiety, a reported use of antidepressant medication, and measurements of epigenetic changes in umbilical cord blood. Studies using genome-wide or candidate-based epigenetic analyses were included. Citations and references from the included articles were investigated to locate further relevant articles. The completeness of reporting as well as the risk of bias and confounding was assessed.
RESULTS
Six studies were included. They all investigated methylation changes. Genome-wide methylation changes were examined in 184 children and methylation status in specific genes was examined in 96 children exposed to antidepressant medication. Three of the studies found an association between use of antidepressant medication during pregnancy and methylation status at various CpG sites measured in cord blood of the newborn. One of these studies found an association in African-Americans, but not Caucasians. The remaining three studies found associations between maternal mood and epigenetic changes in umbilical cord blood but no association between epigenetic changes and maternal use of antidepressant medication.
CONCLUSION
The included studies have not established a clear association between use of antidepressant medication during pregnancy and epigenetic changes in the cord blood. Future studies using newer, more wide-ranging epigenetic methods could discover possible new differentially methylated sites. Larger sample sizes and good validity of exposures are warranted in order to adjust for level of maternal depression, other maternal illness, maternal use of other types of medication, and maternal ethnicity. PROSPERO registration number: CRD42015026575.
Topics: Antidepressive Agents; DNA Methylation; Depression; Epigenesis, Genetic; Female; Fetal Blood; Humans; Maternal Exposure; Pregnancy; Pregnancy Complications
PubMed: 27610205
DOI: 10.1186/s13148-016-0262-x -
Medicine Jun 2016Numerous original clinical studies have attempted to investigate the prognostic value of HER-2 overexpression in osteosarcoma, but the results of these studies are not... (Meta-Analysis)
Meta-Analysis Review
Numerous original clinical studies have attempted to investigate the prognostic value of HER-2 overexpression in osteosarcoma, but the results of these studies are not consistent. This meta-analysis and systematic review was performed to further assess the correlation between HER-2 expression and prognosis in patients with osteosarcoma. A detailed search of relevant publications was conducted using 7 electronic databases: PubMed, Embase, the Cochrane library, the Wanfang database, the China National Knowledge Internet (CNKI) database, the Chinese VIP database, and the Chinese Biological Medical (CBM) Database for publications through August 1, 2015, using the following keywords (HER-2 OR ErbB-2 OR C-erbB-2 OR neu) AND (osteosarcoma OR osteogenic tumor). The bibliographies of potentially relevant articles and identified articles were then searched by hand. Eligible studies were those that enrolled participants with osteosarcoma and provided survival outcome in HER-2 positive and negative groups. The hazard ratio (HR) and 95% confidence interval (CI) for each individual study was calculated and pooled to obtain integrated estimates, using random effects modeling. Sixteen studies involving 934 participants with osteosarcoma met our inclusion criteria. HER-2 overexpression was documented in 42.2% of patients with osteosarcoma. Compared with patients without HER-2 overexpression, those overexpressing HER-2 had decreased overall survival (HR = 2.03, 95% CI: 1.36-3.03, P < 0.001). Statistical associations between HER-2 overexpression and unfavorable overall survival (OS) were observed for both biopsy and surgical removal specimens (HR = 2.07, 95%CI: 1.16-3.72, P = 0.014; and HR = 2.02, 95%CI: 1.10-3.71, P = 0.024). Results for disease-free survival (DFS) were similar. Overexpression of HER-2 is significantly associated with poor outcome for patients with osteosarcoma and should be assessed at diagnosis and after surgery as a prognostic factor. However, larger-scale multicenter clinical studies are needed to further support these findings.
Topics: Biomarkers, Tumor; Biopsy; Bone Neoplasms; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Orthopedic Procedures; Osteosarcoma; Prognosis; Receptor, ErbB-2
PubMed: 27281068
DOI: 10.1097/MD.0000000000003661