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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 -
Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
BMJ Clinical Evidence Mar 2007Acute organophosphorus poisoning occurs after dermal, respiratory, or oral exposure to either low-volatility pesticides (e.g. chlorpyrifos, dimethoate) or... (Review)
Review
INTRODUCTION
Acute organophosphorus poisoning occurs after dermal, respiratory, or oral exposure to either low-volatility pesticides (e.g. chlorpyrifos, dimethoate) or high-volatility nerve gases (e.g. sarin, tabun). Most cases occur in resource-poor countries as a result of occupational or deliberate exposure to organophosphorus pesticides.
METHODS AND OBJECTIVES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute organophosphorus poisoning? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal, alpha2 adrenergic receptor agonists, atropine, benzodiazepines, butyrylcholinesterase replacement therapy, cathartics, extracorporeal clearance, gastric lavage, glycopyrronium bromide, ipecacuanha, magnesium sulphate, milk or other home remedies, N-methyl-D-aspartate receptor antagonists, organophosphorus hydrolases, oximes, sodium bicarbonate, washing the poisoned person and removing contaminated clothing.
Topics: Acute Disease; Administration, Oral; Charcoal; Gastric Lavage; Humans; Organophosphate Poisoning; Oximes; Pesticides; Receptors, N-Methyl-D-Aspartate; Sodium Bicarbonate
PubMed: 19454054
DOI: No ID Found -
BMC Cancer Jan 2011The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with... (Meta-Analysis)
Meta-Analysis Review
O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction.
BACKGROUND
The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP.
METHODS
A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance.
RESULTS
Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value.
CONCLUSIONS
Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.
Topics: Brain Neoplasms; DNA Methylation; Humans; Immunohistochemistry; Neoplasms; O(6)-Methylguanine-DNA Methyltransferase; Polymerase Chain Reaction; Prognosis; Promoter Regions, Genetic
PubMed: 21269507
DOI: 10.1186/1471-2407-11-35 -
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 -
Journal of Inherited Metabolic Disease Nov 2015Newborn screening (NBS) is justified if early intervention is effective in a disorder generally not detected early in life on a clinical basis, and if sensitive and... (Review)
Review
Newborn screening (NBS) is justified if early intervention is effective in a disorder generally not detected early in life on a clinical basis, and if sensitive and specific biochemical markers exist. Experience with NBS for homocystinurias and methylation disorders is limited. However, there is robust evidence for the success of early treatment with diet, betaine and/or pyridoxine for CBS deficiency and good evidence for the success of early betaine treatment in severe MTHFR deficiency. These conditions can be screened in dried blood spots by determining methionine (Met), methionine-to-phenylanine (Met/Phe) ratio, and total homocysteine (tHcy) as a second tier marker. Therefore, we recommend NBS for cystathionine beta-synthase and severe MTHFR deficiency. Weaker evidence is available for the disorders of intracellular cobalamin metabolism. Early treatment is clearly of advantage for patients with the late-onset cblC defect. In the early-onset type, survival and non-neurological symptoms improve but the effect on neurocognitive development is uncertain. The cblC defect can be screened by measuring propionylcarnitine, propionylcarnitine-to-acetylcarnitine ratio combined with the second tier markers methylmalonic acid and tHcy. For the cblE and cblG defects, evidence for the benefit of early treatment is weaker; and data on performance of Met, Met/Phe and tHcy even more limited. Individuals homozygous or compound heterozygous for MAT1A mutations may benefit from detection by NBS using Met, which on the other hand also detects asymptomatic heterozygotes. Clinical and laboratory data is insufficient to develop any recommendation on NBS for the cblD, cblF, cblJ defects, glycineN-methyltransferase-, S-adenosylhomocysteinehydrolase- and adenosine kinase deficiency.
Topics: Acetylcarnitine; Betaine; Carnitine; Homocystinuria; Humans; Infant, Newborn; Methionine; Methylation; Methylenetetrahydrofolate Reductase (NADPH2); Methylmalonic Acid; Neonatal Screening; Practice Guidelines as Topic
PubMed: 25762406
DOI: 10.1007/s10545-015-9830-z -
International Journal of Molecular... Aug 2020Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to... (Review)
Review
Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. , , , , , and were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.
Topics: Cyclooxygenase 2; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Histone Code; Histones; Humans; Interferon-gamma; Interleukin-6; Periodontal Diseases; Receptors, Interleukin-6; Suppressor of Cytokine Signaling 1 Protein; Tumor Necrosis Factor-alpha
PubMed: 32867386
DOI: 10.3390/ijms21176217 -
Clinical Epigenetics Aug 2023Screening plays a key role in secondary prevention of cervical cancer. High-risk human papillomavirus (hrHPV) testing, a highly sensitive test but with limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Screening plays a key role in secondary prevention of cervical cancer. High-risk human papillomavirus (hrHPV) testing, a highly sensitive test but with limited specificity, has become the gold standard frontline for screening programs. Thus, the importance of effective triage strategies, including DNA methylation markers, has been emphasized. Despite the potential reported in individual studies, methylation markers still require validation before being recommended for clinical practice. This systematic review and meta-analysis aimed to evaluate the performance of DNA methylation-based biomarkers for detecting high-grade intraepithelial lesions (HSIL) in hrHPV-positive women.
METHODS
Hence, PubMed, Scopus, and Cochrane databases were searched for studies that assessed methylation in hrHPV-positive women in cervical scrapes. Histologically confirmed HSIL was used as endpoint and QUADAS-2 tool enabled assessment of study quality. A bivariate random-effect model was employed to pool the estimated sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values.
RESULTS
Twenty-three studies were included in this meta-analysis, from which cohort and referral population-based studies corresponded to nearly 65%. Most of the women analyzed were Dutch, and CADM1, FAM19A4, MAL, and miR124-2 were the most studied genes. Pooled sensitivity and specificity were 0.68 (CI 95% 0.63-0.72) and 0.75 (CI 95% 0.71-0.80) for cervical intraepithelial neoplasia (CIN) 2+ detection, respectively. For CIN3+ detection, pooled sensitivity and specificity were 0.78 (CI 95% 0.74-0.82) and 0.74 (CI 95% 0.69-0.78), respectively. For pooled prevalence, PPV for CIN2+ and CIN3+ detection were 0.514 and 0.392, respectively. Furthermore, NPV for CIN2+ and CIN3+ detection were 0.857 and 0.938, respectively.
CONCLUSIONS
This meta-analysis confirmed the great potential of DNA methylation-based biomarkers as triage tool for hrHPV-positive women in cervical cancer screening. Standardization and improved validation are, however, required. Nevertheless, these markers might represent an excellent alternative to cytology and genotyping for colposcopy referral of hrHPV-positive women, allowing for more cost-effective screening programs.
Topics: Female; Humans; Pregnancy; Uterine Cervical Neoplasms; DNA Methylation; Early Detection of Cancer; Colposcopy; Triage; Papillomavirus Infections; Referral and Consultation; Papillomaviridae; Cell Adhesion Molecule-1
PubMed: 37533074
DOI: 10.1186/s13148-023-01537-2 -
PloS One 2017One of the critical mechanisms of gastrointestinal cancer pathogenesis is the silencing of death associated protein kinase 1 (DAPK1), which could be caused by aberrant... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
One of the critical mechanisms of gastrointestinal cancer pathogenesis is the silencing of death associated protein kinase 1 (DAPK1), which could be caused by aberrant methylation of the promoter. However, the relationship between DAPK1 methylation and the risk of gastrointestinal cancer is still controversial. Hence, we conducted this study to determine the potential correlation.
METHODS
Eligible publications were searched in the Pubmed, Embase, and Cochrane Library through November 2016 according to the inclusion criteria and exclusion criteria. Revman 5.3 and Stata 12.0 software were used to analyze the relevant data regarding the association between the frequency of DAPK1 methylation and gastrointestinal cancer.
RESULTS
A total of 22 studies with 2406 patients were included in this meta analysis. Methylation of DAPK1 was positively related with the risk of gastrointestinal cancer (odds ratio [OR] = 5.35, 95% confidence interval [CI]: 2.76-10.38, P<0.00001, random effects model). The source of heterogeneity was analyzed by sensitivity analysis and subgroup analysis. After omitting one heterogeneous study, the I2 decreased and the OR increased in pooled analysis. Also, the heterogeneity decreased most significantly in the subgroup of studies that had a sample size of less than 60 cases. Then, the correlations between DAPK1 methylation and clinicopathological features of gastrointestinal cancer were assessed. DAPK1 methylation was positively correlated with the lymph node (N) stage (positive vs. negative, OR = 1.45, 95%CI: 1.01-2.06, P = 0.04, fixed effects model) and poor differentiation (OR = 1.55, 95%CI: 1.02-2.35, P = 0.04, fixed effects model) in gastric cancer, and the association was significant among Asian patients. However, among cases of gastrointestinal cancer, the association between DAPK1 methylation and tumor (T) stage, N stage, distant metastasis (M) stage, and cancer differentiation were not statistically significant.
CONCLUSIONS
DAPK1 methylation is a potential biomarker for the early diagnosis of gastrointestinal cancer. Further analysis of the clinicopathological features indicated that aberrant methylation of DAPK1 is positively associated with the tumorigenesis of gastrointestinal cancer, and metastasis of gastric cancer.
Topics: DNA Methylation; Death-Associated Protein Kinases; Gastrointestinal Neoplasms; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Risk Factors
PubMed: 28934284
DOI: 10.1371/journal.pone.0184959 -
PloS One 2016Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as... (Review)
Review
IMPORTANCE
Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD).
OBJECTIVE
To systematically review studies investigating epigenetic marks in AD or PD.
METHODS
Eleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form.
RESULTS
Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD.
CONCLUSION
Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.
Topics: Alzheimer Disease; Bias; Cross-Sectional Studies; DNA Methylation; Epigenesis, Genetic; Genome, Human; Histone Code; Histones; Humans; Inflammation; Neurodegenerative Diseases; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 27973581
DOI: 10.1371/journal.pone.0167201