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Biomedicines Feb 2024The () gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted... (Review)
Review
The () gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted reproductive techniques (ART), such as Angelman and Prader-Willi. Data present in the literature suggest the association between aberrant sperm gene methylation and abnormal sperm parameters. The latest meta-analysis on the methylation pattern of this gene in spermatozoa of infertile patients published in 2017 reported a higher degree of methylation in the spermatozoa of infertile patients compared to fertile controls. Here we provide an updated and comprehensive systematic review and meta-analysis of the sperm methylation pattern of the gene in patients with abnormal sperm parameters/infertility compared to men with normal sperm parameters/fertile. For the first time in the literature, we performed a meta-regression analysis to evaluate whether age or sperm concentration could influence the methylation status of this gene at the sperm level. This meta-analysis was registered in PROSPERO (n. CRD42023397056). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the MOOSE guidelines for meta-analyses and systematic reviews of observational studies were strictly followed in our meta-analysis. According to our Population Exposure Comparison Outcome (PECO) question, we included data from original articles assessing the levels of gene methylation at the sperm level in infertile patients or patients with abnormalities in one or more sperm parameters compared to fertile or normozoospermic men. Only six of 354 screened studies were included in the quantitative synthesis. Our analysis showed significantly higher levels of gene methylation in patients compared to controls. However, significant heterogeneity was found between studies. In sensitivity analysis, no studies were sensitive enough to skew the results. The Egger test showed no publication bias. In the meta-regression analysis, the results were independent of age and sperm concentration in the overall population. The same results were found in the control group. However, when analyzing the patient group, a direct correlation was found between methylation and age, indicating that the degree of methylation of the gene increases with advancing age. Fertility status or abnormality of sperm parameters is associated with a change in the methylation pattern of the gene, with higher levels found in infertile patients or those with abnormal sperm parameters compared to fertile men or men with normal sperm parameters. In the group of infertile patients/patients with abnormal sperm parameters, age was directly correlated to the degree of methylation, highlighting the presence of a mechanism that explains the age-related altered sperm quality and the risk of ART. Despite some limitations present in the analyzed studies, our results support the inclusion of methylation in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to analyze in couples who want to undergo ART.
PubMed: 38398047
DOI: 10.3390/biomedicines12020445 -
Frontiers in Medicine 2024Essential oils from various plants have diverse therapeutic properties and are researched extensively. They have applications in medicine, aromatherapy, microbiology,... (Review)
Review
PURPOSE
Essential oils from various plants have diverse therapeutic properties and are researched extensively. They have applications in medicine, aromatherapy, microbiology, agriculture, livestock, and the food industry, benefiting the population.
METHODS
This systematic review followed the PRISMA verification protocol. The study focused on the anti-inflammatory effects, nutraceutical properties, antioxidant and antibacterial activity of essential oils in lemon, orange, cumin, cinnamon, coriander, rosemary, thyme, and parsley. We also looked at their presence in the diet, their effect, their mechanism of action on health, and the most important active compounds. The search was conducted in the PubMed database for the last 12 years of publications, including , , and online cell model tests.
RESULTS
Essential oils have been shown to have multiple health benefits, primarily due to their antimicrobial and anti-inflammatory effects. The mechanism of action of cinnamon oil alters bacterial membranes, modifies lipid profiles, and inhibits cell division, giving a potential benefit in protection against colitis. On the other hand, a significant improvement was observed in the diastolic pressure of patients with metabolic syndrome when supplementing them with cumin essential oil. The antimicrobial properties of coriander essential oil, especially its application in seafood like tilapia, demonstrate efficacy in improving health and resistance to bacterial infections. Cumin essential oil treats inflammation. Parsley essential oil is an antioxidant. Orange peel oil is antibacterial, antifungal, antiparasitic, and pro-oxidative. Lemon essential oil affects mouse intestinal microbiota. Thyme essential oil protects the colon against damage and DNA methylation. Carnosic acid in rosemary oil can reduce prostate cancer cell viability by modifying the endoplasmic reticulum function.
CONCLUSION AND DISCUSSION
Essential oils have many therapeutic and antiparasitic properties. They are beneficial to human health in many ways. However, to understand their potential benefits, more research is needed regarding essential oils such as coriander, parsley, rosemary, cumin, and thyme. These research gaps are relevant since they restrict understanding of the possible benefits of these crucial oils for health-related contexts.
PubMed: 38435393
DOI: 10.3389/fmed.2024.1337785 -
The British Journal of Nutrition Mar 2024Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of... (Review)
Review
Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found.
Topics: Male; Animals; Humans; Phytosterols; Noncommunicable Diseases; Cholesterol; Epigenesis, Genetic; Neoplasms; MicroRNAs; Mammals
PubMed: 37955052
DOI: 10.1017/S0007114523002532 -
Epigenetics Dec 2023Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future...
Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future pregnancy complications. We summarized from the literature all first trimester circulating miRNAs associated with pregnancy complications of placental origin and further identified the miRNAs which have the most evidence as potential early biomarkers for pregnancy complications. We conducted a systematic review following PRISMA reporting guidelines (PROSPERO CRD42020183421). We identified all first trimester serum or plasma miRNAs associated with a pregnancy complication of placental origin (preeclampsia, intrauterine growth restriction (IUGR), gestational hypertension, preterm delivery) and the number of times those miRNAs were identified, as a measure of replication. Twenty-one studies examined 118 unique miRNAs, and 87 were associated with at least one pregnancy complication; preeclampsia was the most common. Seven miRNAs were significantly associated with a pregnancy complication in at least two studies: miR-125b, miR-518b, miR-628-3p, miR-365a-3p, miR-520h, miR-374a-5p, miR-191-5p. Few miRNAs were associated with more than one pregnancy complication: miR-518b and miR-520h with preeclampsia and gestational hypertension, miR-374a-5p and miR-191-5p with preterm birth and preeclampsia. Our systematic review suggests seven miRNAs as potential biomarkers of pregnancy complications. These complications are thought to originate with early placental defects and these miRNAs may also be biomarkers of placental pathology. First-trimester biomarkers of pregnancy complications can facilitate early detection and interventions.
Topics: Pregnancy; Humans; Infant, Newborn; Female; Pregnancy Trimester, First; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Circulating MicroRNA; Placenta; Premature Birth; DNA Methylation; MicroRNAs; Pregnancy Complications; Placentation; Biomarkers
PubMed: 36503407
DOI: 10.1080/15592294.2022.2152615 -
American Journal of Respiratory and... Feb 2024Chronic Obstructive Pulmonary Disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as...
BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. This systematic review synthesizes evidence from epigenome-wide association studies (EWAS) related to COPD and lung function.
METHODS
Systematic literature search on PubMed, Embase and CINAHL databases, identified 1947 articles that investigated epigenetic changes associated with COPD/lung function; 17 of them met our eligibility criteria from which data was manually extracted. Differentially methylated positions (DMPs) and/or annotated genes, were considered replicated if identified by ≥2 studies with a p<1 x 10-4.
RESULTS
Ten studies profiled DNA methylation changes in blood and 7 in respiratory samples, including surgically resected lung tissue (n=3), small airways epithelial brushings (n=2), bronchoalveolar lavage (n=1) and sputum (n=1). Main results showed: (1) high variability in study design, covariates and effect sizes, which prevented a formal meta-analysis; (2) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; (3) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and, (4) in COPD vs. control studies, 123 genes (2.6% of total) were shared between ≥1 blood and ≥1 respiratory sample and associated with chronic inflammation, ion transport and coagulation.
CONCLUSIONS
There is high heterogeneity across published COPD/lung function EWAS studies. A few genes (n=123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research.
PubMed: 38422471
DOI: 10.1164/rccm.202302-0231OC -
Fertility and Sterility Jan 2024Because analytic technologies improve, increasing amounts of data on methylation differences between assisted reproductive technology (ART) and unassisted conceptions... (Review)
Review
IMPORTANCE
Because analytic technologies improve, increasing amounts of data on methylation differences between assisted reproductive technology (ART) and unassisted conceptions are available. However, various studies use different tissue types and different populations in their analyses, making data comparison and integration difficult.
OBJECTIVE
To compare and integrate data on genome-wide analyses of methylation differences due to ART, allowing exposure of overarching themes.
EVIDENCE REVIEW
All studies undertaking genome-wide analysis of human methylation differences due to ART or infertility in any tissue type across the lifespan were assessed for inclusion.
FINDINGS
Seventeen studies were identified that met the inclusion criteria. One study assessed trophectoderm biopsies, 2 first-trimester placenta, 1 first-trimester fetal tissue, 2 term placenta, 7 cord blood, 3 newborn dried blood spots, 1 childhood buccal smears, 1 childhood peripheral blood, and 2 adult peripheral blood. Eleven studies compared tissues from in vitro fertilization (IVF) conceptions with those of unassisted conceptions, 4 compared intracytoplasmic sperm injection with unassisted conceptions, 4 compared non-IVF fertility treatment (NIFT) with unassisted conceptions, 4 compared NIFT with IVF, and 5 compared an infertile population (conceiving via various methods) with an unassisted presumably fertile population. In studies assessing placental tissue, 1 gene with potential methylation changes due to IVF when compared with unassisted conceptions was identified by 2 studies. In blood, 11 potential genes with methylation changes due to IVF compared with unassisted conceptions were identified by 2 studies, 1 of which was identified by 3 studies. Three potentially affected genes were identified by 2 studies involving blood between intracytoplasmic sperm injection and unassisted populations. There were no overlapping genes identified in any tissue type between NIFT and unassisted populations, between NIFT and IVF, or the infertility combined population when compared with the unassisted fertile population.
CONCLUSIONS
Comparing studies is challenging due to differing variables between analyses. However, even in similar tissue types and populations, overlapping methylation changes are limited, suggesting that differences due to ART are minimal.
RELEVANCE
Information from this systematic review is significant for providers and patients who provide and use ART to understand methylation risks that may be associated with the technology.
Topics: Adult; Child; Female; Humans; Infant, Newborn; Male; Pregnancy; DNA Methylation; Fertilization in Vitro; Genome-Wide Association Study; Infertility; Placenta; Reproductive Techniques, Assisted; Semen
PubMed: 37827482
DOI: 10.1016/j.fertnstert.2023.10.007 -
EClinicalMedicine Apr 2024Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small...
BACKGROUND
Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small for GA at a population level. Currently, the gold standard for pregnancy dating is measurement of the fetal crown rump length at 11-14 weeks of gestation. However, this is not possible for women first presenting in later pregnancy, or in settings where routine ultrasound is not available. A reliable, cheap and easy to measure GA-dependent biomarker would provide an important breakthrough in estimating the age of pregnancy. Therefore, the aim of this study was to determine the accuracy of prenatal and postnatal biomarkers for estimating gestational age (GA).
METHODS
Systematic review prospectively registered with PROSPERO (CRD42020167727) and reported in accordance with the PRISMA-DTA. Medline, Embase, CINAHL, LILACS, and other databases were searched from inception until September 2023 for cohort or cross-sectional studies that reported on the accuracy of prenatal and postnatal biomarkers for estimating GA. In addition, we searched Google Scholar and screened proceedings of relevant conferences and reference lists of identified studies and relevant reviews. There were no language or date restrictions. Pooled coefficients of correlation and root mean square error (RMSE, average deviation in weeks between the GA estimated by the biomarker and that estimated by the gold standard method) were calculated. The risk of bias in each included study was also assessed.
FINDINGS
Thirty-nine studies fulfilled the inclusion criteria: 20 studies (2,050 women) assessed prenatal biomarkers (placental hormones, metabolomic profiles, proteomics, cell-free RNA transcripts, and exon-level gene expression), and 19 (1,738,652 newborns) assessed postnatal biomarkers (metabolomic profiles, DNA methylation profiles, and fetal haematological components). Among the prenatal biomarkers assessed, human chorionic gonadotrophin measured in maternal serum between 4 and 9 weeks of gestation showed the highest correlation with the reference standard GA, with a pooled coefficient of correlation of 0.88. Among the postnatal biomarkers assessed, metabolomic profiling from newborn blood spots provided the most accurate estimate of GA, with a pooled RMSE of 1.03 weeks across all GAs. It performed best for term infants with a slightly reduced accuracy for preterm or small for GA infants. The pooled RMSEs for metabolomic profiling and DNA methylation profile from cord blood samples were 1.57 and 1.60 weeks, respectively.
INTERPRETATION
We identified no antenatal biomarkers that accurately predict GA over a wide window of pregnancy. Postnatally, metabolomic profiling from newborn blood spot provides an accurate estimate of GA, however, as this is known only after birth it is not useful to guide antenatal care. Further prenatal studies are needed to identify biomarkers that can be used in isolation, as part of a biomarker panel, or in combination with other clinical methods to narrow prediction intervals of GA estimation.
FUNDING
The research was funded by the Bill and Melinda Gates Foundation (INV-000368). ATP is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre funding scheme. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, the Department of Health, or the Department of Biotechnology. The funders of this study had no role in study design, data collection, analysis or interpretation of the data, in writing the paper or the decision to submit for publication.
PubMed: 38495518
DOI: 10.1016/j.eclinm.2024.102498 -
Translational Psychiatry Jul 2023Obsessive-compulsive disorder (OCD) is a frequent and debilitating mental illness. Although efficacious treatment options are available, treatment resistance rates are...
Obsessive-compulsive disorder (OCD) is a frequent and debilitating mental illness. Although efficacious treatment options are available, treatment resistance rates are high. Emerging evidence suggests that biological components, especially autoimmune processes, may be associated with some cases of OCD and treatment resistance. Therefore, this systematic literature review summarizing all case reports/case series as well as uncontrolled and controlled cross-sectional studies investigating autoantibodies in patients with OCD and obsessive-compulsive symptoms (OCS) was performed. The following search strategy was used to search PubMed: "(OCD OR obsessive-compulsive OR obsessive OR compulsive) AND (antib* OR autoantib* OR auto-antib* OR immunoglob* OR IgG OR IgM OR IgA)". Nine case reports with autoantibody-associated OCD/OCS were identified: five patients with anti-neuronal autoantibodies (against N-methyl-D-aspartate-receptor [NMDA-R], collapsin response mediator protein [CV2], paraneoplastic antigen Ma2 [Ma2], voltage gated potassium channel complex [VGKC], and "anti-brain" structures) and four with autoantibodies associated with systemic autoimmune diseases (two with Sjögren syndrome, one with neuropsychiatric lupus, and one with anti-phospholipid autoantibodies). Six patients (67%) benefited from immunotherapy. In addition, eleven cross-sectional studies (six with healthy controls, three with neurological/psychiatric patient controls, and two uncontrolled) were identified with inconsistent results, but in six studies an association between autoantibodies and OCD was suggested. In summary, the available case reports suggest an association between OCD and autoantibodies in rare cases, which has been supported by initial cross-sectional studies. However, scientific data is still very limited. Thus, further studies on autoantibodies investigated in patients with OCD compared with healthy controls are needed.
Topics: Humans; Autoantibodies; Cross-Sectional Studies; Obsessive-Compulsive Disorder; Receptors, N-Methyl-D-Aspartate; Brain
PubMed: 37400462
DOI: 10.1038/s41398-023-02545-9 -
Psychopharmacology Oct 2023Nitrous oxide (NO) has been initially confirmed by clinical trials to benefit to patients with major depressive disorder (MDD). However, there needs to be a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nitrous oxide (NO) has been initially confirmed by clinical trials to benefit to patients with major depressive disorder (MDD). However, there needs to be a meta-analysis to compare the efficacy and tolerability of NO in MDD.
METHODS
PubMed, EMBASE, and Cochrane Library were searched for relevant studies up to Jan 1st, 2023. The meta-analysis mainly compared the outcome of the change in depression severity scores, response, remission, and adverse events in patients with MDD receiving 50% NO and placebo.
RESULTS
Four studies with 133 patients were eventually identified. We found that the NO group and control group showed an overall significant difference in the change in depression severity score for patients at 2 h, 24 h, and 2 weeks or more (2 h, SMD = - 0.64, 95% CI - 0.01 to - 0.28, p < 0.0001) (24 h, SMD = - 0.65, 95% CI - 1.01 to - 0.29, p < 0.0001) (2 weeks, SMD = - 0.76, 95% CI - 1.16 to - 0.36, p < 0.0001). For the response and remission rate, the long-term effect of NO was also statistically significant (for the response, RR = 2.33, 95% CI 1.23 to 4.44, p = 0.01) (for the remission, RR = 4.68, 95% CI 1.49 to 14.68, p = 0.008). For safety outcomes, patients treated with NO had higher odds of nausea or vomiting (RR = 10.15, 95% CI 1.96 to 52.59, p = 0.009).
CONCLUSION
Our study suggested that NO has a rapid and long-lasting antidepressant effect in patients with MDD. However, the efficacy of lower or titrated concentration of N2O should be further investigated.
Topics: Humans; Depressive Disorder, Major; Nitrous Oxide; Nausea; Vomiting
PubMed: 37608194
DOI: 10.1007/s00213-023-06449-w -
Environmental and Molecular Mutagenesis Aug 2023Individual differences in drug response have always existed in clinical treatment. Many non-genetic factors show non-negligible impacts on personalized medicine.... (Review)
Review
Individual differences in drug response have always existed in clinical treatment. Many non-genetic factors show non-negligible impacts on personalized medicine. Emerging studies have demonstrated epigenetic could connect non-genetic factors and individual treatment differences. We used systematic retrieval methods and reviewed studies that showed individual factors' impact on DNA methylation of drug metabolism genes. In total, 68 studies were included, and half (n = 36) were cohort studies. Six aspects of individual factors were summarized from the perspective of personalized medicine: parental exposure, environmental pollutants exposure, obesity and diet, drugs, gender and others. The most research (n = 11) focused on ABCG1 methylation. The majority of studies showed non-genetic factors could result in a significant DNA methylation alteration in drug metabolism genes, which subsequently affects the pharmacokinetic processes. However, the underlying mechanism remained unknown. Finally, some viewpoints were presented for future research.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Diet
PubMed: 37522536
DOI: 10.1002/em.22567