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Lifestyle Genomics 2023DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear.
OBJECTIVES
The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation.
METHODS
A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation.
RESULTS
Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as "high risk" or "some concerns." Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo.
CONCLUSION
Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.
Topics: Humans; Animals; DNA Methylation; Folic Acid; Dietary Supplements; Vitamin B Complex; Micronutrients
PubMed: 37935134
DOI: 10.1159/000533193 -
Cells Jul 2023Osteoarthritis (OA) is a joint disorder characterized by progressive degeneration of cartilage extracellular matrix (ECM), chondrocyte hypertrophy and apoptosis and... (Review)
Review
Epigenetic Modifications of MiRNAs in Osteoarthritis: A Systematic Review on Their Methylation Levels and Effects on Chondrocytes, Extracellular Matrix and Joint Inflammation.
Osteoarthritis (OA) is a joint disorder characterized by progressive degeneration of cartilage extracellular matrix (ECM), chondrocyte hypertrophy and apoptosis and inflammation. The current treatments mainly concern pain control and reduction of inflammation, but no therapeutic strategy has been identified as a disease-modifying treatment. Therefore, identifying specific biomarkers useful to prevent, treat or distinguish the stages of OA disease has become an immediate need of clinical practice. The role of microRNAs (miRNAs) in OA has been investigated in the last decade, and increasing evidence has emerged that the influence of the environment on gene expression through epigenetic processes contributes to the development, progression and aggressiveness of OA, in particular acting on the microenvironment modulations. The effects of epigenetic regulation, particularly different miRNA methylation during OA disease, were highlighted in the present systematic review. The evidence arising from this study of the literature conducted in three databases (PubMed, Scopus, Web of Science) suggested that miRNA methylation state already strongly impacts OA progression, driving chondrocytes and synoviocyte proliferation, apoptosis, inflammation and ECM deposition. However, the possibility of understanding the mechanism by which different epigenetic modifications of miRNA or pre-miRNA sequences drive the aggressiveness of OA could be the new focus of future investigations.
Topics: Humans; Chondrocytes; MicroRNAs; Epigenesis, Genetic; Methylation; Osteoarthritis; Inflammation; Extracellular Matrix
PubMed: 37508486
DOI: 10.3390/cells12141821 -
Frontiers in Oncology 2022Pediatric and adult K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from...
INTRODUCTION
Pediatric and adult K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from published studies to investigate the differences between these two groups.
METHODS
PubMed and Web of Science were searched for potential data. Studies were included if they had available individual participant data on patients age of K27M-mutant midline gliomas. For time-to-event analyses, Kaplan-Meier analysis and Cox regression models were carried out; corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of age and clinical covariates on progression-free survival (PFS) and overall survival (OS).
RESULTS
We included 43 studies comprising 272 adults and 657 pediatric midline gliomas with K27M mutation for analyses. In adults, there was a male predilection whereas females were slightly more common than males in the pediatric group. Spinal cord tumors were more frequent in adults. The prevalence of K27M mutation was significantly higher in the pediatric cohort. Compared to adult patients, pediatric K27M-mutant midline gliomas exhibited more aggressive features including higher rates of pathologic features of high-grade tumors and Ki67 proliferation index, and had a shorter PFS and OS. Genetically, mutations were more common whereas methylation, , and mutations were less prevalent in the pediatric cohort.
CONCLUSION
Pediatric K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms.
PubMed: 35371982
DOI: 10.3389/fonc.2022.858148 -
Journal of Clinical Anesthesia Nov 2023The objective of this systematic review was to estimate the relative risk of prolonged times to tracheal extubation with desflurane versus sevoflurane or isoflurane.... (Meta-Analysis)
Meta-Analysis Review
The objective of this systematic review was to estimate the relative risk of prolonged times to tracheal extubation with desflurane versus sevoflurane or isoflurane. Prolonged times are defined as ≥15 min from end of surgery (or anesthetic discontinuation) to extubation in the operating room. They are associated with reintubations, naloxone and flumazenil administration, longer times from procedure end to operating room exit, greater differences between actual and scheduled operating room times, longer times from operating room exit to next case start, longer durations of the workday, and more operating room personnel idle while waiting for extubation. Published randomized clinical trials of humans were included. Generalized pivotal methods were used to estimate the relative risk of prolonged extubation for each study from reported means and standard deviations of extubation times. The relative risks were combined using DerSimonian-Laird random effects meta-analysis with Knapp-Hartung adjustment. From 67 papers, there were 78 two-drug comparisons, including 5167 patients. Studies were of high quality (23/78) or moderate quality (55/78), the latter due to lack of blinding of observers to group assignment and/or patient attrition because patients were extubated after operating room exit. Desflurane resulted in a 65% relative reduction in the incidence of prolonged extubation compared with sevoflurane (95% confidence interval 49% to 76%, P < .0001) and in a 78% relative reduction compared with isoflurane (58% to 89%, P = .0001). There were no significant associations between studies' relative risks and quality, industry funding, or year of publication (all six meta-regressions P ≥ .35). In conclusion, when emergence from general anesthesia with different drugs are compared with sevoflurane or isoflurane, suitable benchmarks quantifying rapidity of emergence are reductions in the incidence of prolonged extubation achieved by desflurane, approximately 65% and 78%, respectively. These estimates give realistic context for interpretation of results of future studies that compare new anesthetic agents to current anesthetics.
Topics: Humans; Isoflurane; Sevoflurane; Desflurane; Risk; Airway Extubation; Anesthetics, Inhalation; Methyl Ethers; Anesthesia Recovery Period
PubMed: 37481911
DOI: 10.1016/j.jclinane.2023.111210 -
Frontiers in Pediatrics 2022The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are...
BACKGROUND
The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are poorly understood. We aimed to synthesize the current knowledge of the association of sedentary behavior and physical activity (acute and chronic effects) with gene expression and epigenetic modifications in children and adolescents.
METHODS
PubMed, Web of Science, and Scopus databases were systematically searched until April 2022. A total of 15 articles were eligible for this review. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews and/or a modified version of the Downs and Black checklist.
RESULTS
Thirteen studies used candidate gene approach, while only 2 studies performed high-throughput analyses. The candidate genes significantly linked to sedentary behavior or physical activity were: , , -α, , , , and . Non-coding Ribonucleic acids (RNAs) regulated by sedentary behavior or physical activity were: miRNA-222, miRNA-146, miRNA-16, miRNA-126, miR-320, and long non-coding RNA MALAT1. These molecules are involved in inflammation, immune function, angiogenic process, and cardiovascular disease. Transcriptomics analyses detected thousands of genes that were altered following an acute bout of physical activity and are linked to gene pathways related to immune function, apoptosis, and metabolic diseases.
CONCLUSION
The evidence found to date is rather limited. Multidisciplinary studies are essential to characterize the molecular mechanisms in response to sedentary behavior and physical activity in the pediatric population. Larger cohorts and randomized controlled trials, in combination with multi-omics analyses, may provide the necessary data to bring the field forward.
SYSTEMATIC REVIEW REGISTRATION
[www.ClinicalTrials.gov], identifier [CRD42021235431].
PubMed: 35813370
DOI: 10.3389/fped.2022.917152 -
Genes Feb 2023Chronic pain represents a major global health issue in terms of psycho-physiological, therapeutic, and economic burden, not limited to adults but also to the pediatric... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Chronic pain represents a major global health issue in terms of psycho-physiological, therapeutic, and economic burden, not limited to adults but also to the pediatric age. Despite its great impact, its molecular mechanisms have still not been completely unraveled. Focusing on the impact of epigenetics in the pain complex trait, we assessed the association between chronic pain and the methylation pattern of TRPA1, a key gene related to pain sensitivity.
METHODS
We conducted a systematic review retrieving articles from three different databases. After deduplication, 431 items were subjected to manual screening, and then 61 articles were selected and screened again. Of these, only six were maintained for meta-analysis and analyzed using specific R packages.
RESULTS
Six articles were divided into two groups (group 1: comparison of mean methylation levels between healthy subjects and patients with chronic pain; group 2: correlation between mean methylation levels and pain sensation). A non-significant mean difference was obtained from the analysis of group 1 with a value of 3.97 (95% C.I. -7.79; 15.73). Analysis of group 2 showed a high level of variability between studies (correlation = 0.35, 95% C.I. -0.12; 0.82) due to their heterogeneity (I = 97%, < 0.01).
CONCLUSIONS
Despite the high variability observed in the different studies analyzed, our results suggest that hypermethylation and increased pain sensitivity could be connected, possibly due to the variation of TRPA1 expression.
Topics: Adult; Child; Humans; Ankyrins; Chronic Pain; DNA Methylation; Epigenesis, Genetic; TRPA1 Cation Channel
PubMed: 36833338
DOI: 10.3390/genes14020411 -
Journal of Pharmacy & Pharmaceutical... 2022Till date, only systemic corticosteroids have demonstrated definite mortality benefit in management of COVID 19 in various studies. Still certain questions regarding the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Till date, only systemic corticosteroids have demonstrated definite mortality benefit in management of COVID 19 in various studies. Still certain questions regarding the appropriate dose, duration and timing of corticosteroids remain unanswered. For this reason, the study was planned to determine the efficacy and safety of the pulse dose methyl prednisolone in management of COVID 19 from the publicly available evidence.
METHODS
PubMed, the Cochrane library, ClinicalTrials.gov and medRxiv were searched for articles reporting the use of pulse dose methyl prednisolone in COVID 19 from inception till 31st May, 2021. Odds ratios (ORs) were calculated for estimation of pooled effect by using random effect model and heterogeneity was checked by using I2 statistics.
RESULTS
Twelve studies (11 observational and 1 RCT) were included in the systematic review. A total of 3110 patients from 9 studies were included in the meta-analysis. Though the use of pulse dose methyl prednisolone demonstrated statistically significant mortality benefit in comparison to usual care (OR=0.71, 95% CI: 0.51 to 0.97, [P=0.03]), (I2= 21%) with calculated Number needed to treat (NNT) of 23.5, there was no statistically significant difference between the use of pulse dose and low dose corticosteroid (OR=0.66, 95% CI: 0.44 to 1.01, [(P=0.05]), (I2= 25%) and the NNT is 23.5. Incidence of adverse events were similar across all the groups. The grade of evidence for primary outcome was of moderate certainty.
CONCLUSION
This meta-analysis concurs with the previous reports regarding the use of corticosteroid in COVID 19 in comparison to usual care. However, for both the primary and secondary outcome, the study did not find any statistically significant difference between the use of pulse dose methyl prednisolone and low dose corticosteroid to treat COVID 19 patients.
Topics: Adrenal Cortex Hormones; Humans; Methylprednisolone; COVID-19 Drug Treatment
PubMed: 35364003
DOI: 10.18433/jpps32430 -
Neurology. Clinical Practice Aug 2021There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose... (Review)
Review
BACKGROUND
There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose of this review is to evaluate the clinical utility of blood-based biomarkers in patients with SMA.
METHODS
A systematic review of MEDLINE, DARE, PEDro, PsycINFO, Cochrane Database, LILACS, OTSeeker, SpeechBITE, CINAHL, Scopus, Science Direct, clinicaltrial.gov, OpenGrey, and Google Scholar was performed with the last search data of June 30, 2019.
RESULTS
Survival motor neuron (SMN)-related biomarkers showed an important interpatient and cell variability with a wide overlap between SMA phenotypes and healthy controls. Several plasma protein analytes correlated with motor scores; however, validation studies are needed to rule out false positives. DNA methylation analysis distinguished between patients with mild/moderate SMA and healthy controls. Plasma phosphorylated neurofilament heavy chain (pNF-H) levels increased with disease severity and declined considerably after nusinersen treatment.
CONCLUSION
There is no sufficient evidence to support the clinical utility of SMN-related biomarkers to predict disease severity in SMA. pNF-H appears to be a promising biomarker of disease activity and treatment effect in SMA. Further studies should include longitudinal assessments of patients with SMA across functional groups and comparisons with age-matched healthy controls to evaluate the stability of putative biomarkers over time and in response to SMA therapeutics. PROSPERO registration: CRD42019139050.
PubMed: 34484951
DOI: 10.1212/CPJ.0000000000000872 -
Journal of Psychiatric Research Apr 2024This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs)... (Meta-Analysis)
Meta-Analysis Review
The effect of N-methyl-D-aspartate receptor antagonists on the mismatch negativity of event-related potentials and its regulatory factors: A systematic review and meta-analysis.
This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs) in healthy subjects and explores whether NMDAR antagonists have different effects on MMN components under different types of antagonists, drug dosages, and deviant stimuli. We conducted a comprehensive literature search of PubMed, EMBASE, and the Cochrane Library from inception to August 1, 2023 for studies comparing the MMN components between the NMDAR antagonist intervention group and the control group (or baseline). All statistical analyses were performed using Stata version 12.0 software. Sixteen articles were included in the systematic review: 13 articles were included in the meta-analysis of MMN amplitudes, and seven articles were included in the meta-analysis of MMN latencies. The pooled analysis showed that NMDAR antagonists reduced MMN amplitudes [SMD (95% CI) = 0.32 (0.16, 0.47), P < 0.01, I = 47.3%, p < 0.01] and prolonged MMN latencies [SMD (95% CI) = 0.31 (0.13, 0.49), P = 0.16, I = 28.3%, p < 0.01]. The type of antagonist drug regulates the effect of NMDAR antagonists on MMN amplitudes. Different antagonists, doses of antagonists, and types of deviant stimuli can also have different effects on MMN. These findings indicate a correlation between NMDAR and MMN, which may provide a foundation for the application of ERP-MMN in the early identification of NMDAR encephalitis.
Topics: Humans; Receptors, N-Methyl-D-Aspartate; Evoked Potentials, Auditory; Electroencephalography; Evoked Potentials; Acoustic Stimulation
PubMed: 38402843
DOI: 10.1016/j.jpsychires.2024.02.004 -
Epigenetics Apr 2022When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such...
When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such modifications occur and whether they disrupt normal foetal developme nt, are currently unanswered questions. This field of prenatal pharmacoepigenetics has received increasing attention, with several studies reporting associations between medication exposure and offspring epigenetic outcomes. Nevertheless, no recent systematic review of the literature is available. Therefore, the objectives of this review were to (i) provide an overview of the literature on the association of prenatal exposure to psychotropics a nd analgesics with epigenetic outcomes, and (ii) suggest recommendations for future studies within prenatal pharmacoepigenetics. We performed systematic literature searches in five databases. The eligible studies assessed human prenatal exposure to psychotropics or analgesics, with epigenetic analyses of offspring tissue as an outcome. We identified 18 eligible studies including 4,419 neonates exposed to either antidepressants, antiepileptic drugs, paracetamol, acetylsalicylic acid, or methadone. The epigenetic outcome in all studies was DNA methylation in cord blood, placental tissue or buccal cells. Although most studies found significant differences in DNA methylation upon medication exposure, almost no differences were persistent across studies for similar medications and sequencing methods. The reviewed studies were challenging to compare due to poor transparency in reporting, and heterogeneous methodology, design, genome coverage, and statistical modelling. We propose 10 recommendations for future prenatal pharmacoepigenetic studies considering both epidemiological and epigenetic perspectives. These recommendations may improve the quality, comparability, and clinical relevance of such studies. PROSPERO registration ID: CRD42020166675.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Female; Humans; Infant, Newborn; Mouth Mucosa; Placenta; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 33926354
DOI: 10.1080/15592294.2021.1903376