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Clinical Epigenetics Sep 2023Undernutrition in pregnant women is an unfavorable environmental condition that can affect the intrauterine development via epigenetic mechanisms and thus have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Undernutrition in pregnant women is an unfavorable environmental condition that can affect the intrauterine development via epigenetic mechanisms and thus have long-lasting detrimental consequences for the mental health of the offspring later in life. One epigenetic mechanism that has been associated with mental disorders and undernutrition is alterations in DNA methylation. The effect of prenatal undernutrition on the mental health of adult offspring can be analyzed through quasi-experimental studies such as famine studies. The present systematic review and meta-analysis aims to analyze the association between prenatal famine exposure, DNA methylation, and mental disorders in adult offspring. We further investigate whether altered DNA methylation as a result of prenatal famine exposure is prospectively linked to mental disorders.
METHODS
We conducted a systematic search of the databases PubMed and PsycINFO to identify relevant records up to September 2022 on offspring whose mothers experienced famine directly before and/or during pregnancy, examining the impact of prenatal famine exposure on the offspring's DNA methylation and/or mental disorders or symptoms.
RESULTS
The systematic review showed that adults who were prenatally exposed to famine had an increased risk of schizophrenia and depression. Several studies reported an association between prenatal famine exposure and hyper- or hypomethylation of specific genes. The largest number of studies reported differences in DNA methylation of the IGF2 gene. Altered DNA methylation of the DUSP22 gene mediated the association between prenatal famine exposure and schizophrenia in adult offspring. Meta-analysis confirmed the increased risk of schizophrenia following prenatal famine exposure. For DNA methylation, meta-analysis was not suitable due to different microarrays/data processing approaches and/or unavailable data.
CONCLUSION
Prenatal famine exposure is associated with an increased risk of mental disorders and DNA methylation changes. The findings suggest that changes in DNA methylation of genes involved in neuronal, neuroendocrine, and immune processes may be a mechanism that promotes the development of mental disorders such as schizophrenia and depression in adult offspring. Such findings are crucial given that undernutrition has risen worldwide, increasing the risk of famine and thus also of negative effects on mental health.
Topics: Pregnancy; Adult; Female; Humans; DNA Methylation; Famine; Mental Disorders; Vitamins; Malnutrition
PubMed: 37716973
DOI: 10.1186/s13148-023-01557-y -
Seizure Oct 2021Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated antibodies, and AE-related seizures are still unclear.
AIMS
This research evaluated the relationship between AE, AE-related seizures, and neuronal antibodies, as well as the morbidity of AE with early incidence.
METHODS
The PubMed, Embase, Cochrane, and Web of Science databases were searched. Pooled estimates and 95% confidence intervals (CIs) were calculated using a random-effects model.
RESULTS
Of the 4,869 citations identified, 100 articles were reviewed in full, and 42 subgroups were analyzed. The overall incidence of AE patients with seizures was 42% (95% CI: 0.40-0.44), and among them, the incidence of epilepsy in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients was 73% (95% CI: 0.70-0.77). Subsequently, we found that the prevalence of AE as the cause of epilepsy within the pooled period was 1% (95% CI: 0.01-0.02), while the overall positive rate of neuronal antibodies in epilepsy patients was 4% (95% CI: 0.03-0.05). Additionally, the detection rates of different antibodies among epilepsy patients were as follows: anti-NMDAR, 1%; anti-leucine-rich glioma inactivated 1 (LGI1), 1%; anti-contactin-associated protein-like 2 (CASPR2), 2%.
CONCLUSION
Based on our findings, neuronal antibodies may serve as a bridge to study AE and immune-related epilepsy. To further understand the differences in outcomes following different treatment measures, and to provide more information for public health policy and prevention, more research is needed to improve the accuracy of estimations.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Encephalitis; Epilepsy; Hashimoto Disease; Humans
PubMed: 34284303
DOI: 10.1016/j.seizure.2021.07.005 -
Epigenetics Sep 2022Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a...
Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 region of the gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 . Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 region of the gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.
Topics: DNA Methylation; Exons; Female; Humans; Infant; Infant, Newborn; Pregnancy; Protein Processing, Post-Translational; Receptors, Glucocorticoid
PubMed: 34519616
DOI: 10.1080/15592294.2021.1980691 -
Cells Nov 2023There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past... (Review)
Review
There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.
Topics: Humans; Heart Ventricles; Epigenesis, Genetic; Ventricular Dysfunction, Right; Myocardium; Ventricular Function, Right
PubMed: 38067121
DOI: 10.3390/cells12232693 -
Biomedicines Feb 2023A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic... (Review)
Review
A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic marks are reversible but stable regulators of gene expression with utility as biomarkers and therapeutic targets. We aimed to identify and assess all published human studies of epigenetic mechanisms in NS. PubMed (MEDLINE) and Embase were searched for original research articles examining any epigenetic mechanism in samples collected from people with steroid resistant NS, steroid sensitive NS, focal segmental glomerulosclerosis or minimal change disease. Study quality was assessed by using the Joanna Briggs Institute critical appraisal tools. Forty-nine studies met our inclusion criteria. The majority of these examined micro-RNAs ( = 35, 71%). Study quality was low, with only 23 deemed higher quality, and most of these included fewer than 100 patients and failed to validate findings in a second cohort. However, there were some promising concordant results between the studies; higher levels of serum miR-191 and miR-30c, and urinary miR-23b-3p and miR-30a-5p were observed in NS compared to controls. We have identified that the epigenome, particularly DNA methylation and histone modifications, has been understudied in NS. Large clinical studies, which utilise the latest high-throughput technologies and analytical pipelines, should focus on addressing this critical gap in the literature.
PubMed: 36831050
DOI: 10.3390/biomedicines11020514 -
International Journal of Surgery... Apr 2023Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early...
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications.
MAIN RESULTS
Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection.
CONCLUSION
Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.
Topics: Humans; Prospective Studies; Artificial Intelligence; Quality of Life; Biomarkers, Tumor; Early Detection of Cancer; DNA; Cell-Free Nucleic Acids; Colorectal Neoplasms
PubMed: 36974713
DOI: 10.1097/JS9.0000000000000260 -
Translational Psychiatry Feb 2021Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis... (Review)
Review
Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis that maltreatment is associated with epigenetic changes that may subsequently serve as mechanisms of disease. The current review uses a systematic approach to identify and summarize the literature related to childhood maltreatment and alterations in DNA methylation in humans. A total of 100 empirical articles were identified in our systematic review of research published prior to or during March 2020, including studies that focused on candidate genes and studies that leveraged epigenome-wide data in both children and adults. Themes arising from the literature, including consistent and inconsistent patterns of results, are presented. Several directions for future research, including important methodological considerations for future study design, are discussed. Taken together, the literature on childhood maltreatment and DNA methylation underscores the complexity of transactions between the environment and biology across development.
Topics: Adult; Child; Child Abuse; DNA Methylation; Epigenesis, Genetic; Epigenome; Humans; Risk Factors
PubMed: 33608499
DOI: 10.1038/s41398-021-01207-y -
BMJ Open Ophthalmology 2019Rare ophthalmic diseases have a devastating impact on a patient's vision and consequently negatively affect their independence, ability to work and overall quality of... (Review)
Review
Rare ophthalmic diseases have a devastating impact on a patient's vision and consequently negatively affect their independence, ability to work and overall quality of life. Methylation is an important emerging biomarker of disease and may improve understanding of rare ophthalmic disorders. This systematic review sought to identify and evaluate literature on methylation and rare ophthalmic disease. MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and grey literature resources were searched for publications prior to 20 August 2019. Articles written in English which featured key terms such as 'methylation' and rare ophthalmic diseases were included. Titles, abstracts, keywords and full texts of publications were screened, as well as reference lists for reverse citations and Web of Science 'cited reference search' for forward citation searching. Study characteristics were extracted, and methodological rigour appraised using a standardised template. Fourteen articles were selected for full inclusion. Rare ophthalmic conditions include congenital fibrosis of extraocular muscles, retinitis pigmentosa, Fuchs endothelial corneal dystrophy, granular corneal dystrophy, choroideraemia, brittle cornea syndrome, retinopathy of prematurity, keratoconus and congenital cataracts. Outcomes include identification of methylation as contributor to disease and identification of potential novel therapeutic targets. The studies included were heterogeneous with no scope for meta-analysis following review; a narrative synthesis was undertaken. Differential methylation has been identified in a small number of rare ophthalmic diseases and few studies have been performed to date. Further multiomic research will improve understanding of rare eye diseases and hopefully lead to improved provision of diagnostic/prognostic biomarkers, and help identify novel therapeutic targets.
PubMed: 31799411
DOI: 10.1136/bmjophth-2019-000342 -
Cell Death Discovery Apr 2024Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and... (Review)
Review
Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.
PubMed: 38589350
DOI: 10.1038/s41420-024-01935-2 -
Brain & Spine 2022Cystic glioblastoma is a well-recognised clinical entity but the characteristics and role of these cystic components in determining clinical outcome remains poorly...
INTRODUCTION
Cystic glioblastoma is a well-recognised clinical entity but the characteristics and role of these cystic components in determining clinical outcome remains poorly understood.
RESEARCH QUESTION
To determine whether (1) there is a prognostic significance to a glioblastoma having a cystic component and (2) whether the presence of cyst, and its prognosis relative to non-cystic glioblastoma, relates to patient demographics and other tumour characteristics.
MATERIAL & METHODS
A systematic review and meta-analysis was conducted in accordance to PRISMA guidelines. Articles with histological and/or radiological diagnosis of cystic glioblastoma that reported on survival outcome and/or characteristics of cystic glioblastomas mentioned were included. Meta-analysis was performed and presented using random effect model.
RESULTS
Twenty studies met the inclusion criteria, and nine studies were included in the meta-analysis (374 glioblastoma patients with cystic components and 2477 glioblastoma patients without cystic components above 18 years of age). Search result did not yield any Level I evidence. There is statistically significant survival benefit in cystic over non-cystic glioblastomas (HR = 0.81, 95%CI 0.70-0.93, p = 0.004, I = 50%). Studies reported younger average patient age, larger tumor size and slower tumor growth velocity in cystic glioblastoma. No significant difference in gender ratio and IDH-1 and MGMT methylation status between cystic and non-cystic glioblastoma were reported.
DISCUSSION & CONCLUSION
Presence of cyst in glioblastoma tumor is associated with improved overall survival outcome. Etiology of cystic entities and why they might confer survival benefits remained to be determined, and future studies examining how to best treat cystic glioblastomas would be clinically valuable.
PubMed: 36605383
DOI: 10.1016/j.bas.2022.101692