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EBioMedicine May 2024This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective.
METHODS
Using a newly developed Air Pollutants Exposure Score (APES), we utilized a prospective cohort study (UK Biobank) to investigate the associations of individual and combined air pollution exposures with CRC incidence and survival, followed by an up-to-date systematic review with meta-analysis to verify the associations. In epigenetic two-sample Mendelian randomization analyses, we examine the associations between genetically predicted DNA methylation related to air pollution and CRC risk. Further genetic colocalization and gene-environment interaction analyses provided different insights to disentangle pathogenic effects of air pollution via epigenetic modification.
FINDINGS
During a median 12.97-year follow-up, 5767 incident CRC cases among 428,632 participants free of baseline CRC and 533 deaths in 2401 patients with CRC were documented in the UK Biobank. A higher APES score was associated with an increased CRC risk (HR, 1.03, 95% CI = 1.01-1.06; P = 0.016) and poorer survival (HR, 1.13, 95% CI = 1.03-1.23; P = 0.010), particularly among participants with insufficient physical activity and ever smokers (P > 0.05). A subsequent meta-analysis of seven observational studies, including UK Biobank data, corroborated the association between PM exposure (per 10 μg/m increment) and elevated CRC risk (RR,1.42, 95% CI = 1.12-1.79; P = 0.004; I = 90.8%). Genetically predicted methylation at PM-related CpG site cg13835894 near TMBIM1/PNKD and cg16235962 near CXCR5, and NO-related cg16947394 near TMEM110 were associated with an increased CRC risk. Gene-environment interaction analysis confirmed the epigenetic modification of aforementioned CpG sites with CRC risk and survival.
INTERPRETATION
Our study suggests the association between air pollution and CRC incidence and survival, underscoring the possible modifying roles of epigenomic factors. Methylation may partly mediate pathogenic effects of air pollution on CRC, with annotation to epigenetic alterations in protein-coding genes TMBIM1/PNKD, CXCR5 and TMEM110.
FUNDING
Xue Li is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), the National Nature Science Foundation of China (No. 82204019) and Healthy Zhejiang One Million People Cohort (K-20230085). ET is supported by a Cancer Research UK Career Development Fellowship (C31250/A22804). MGD is supported by the MRC Human Genetics Unit Centre Grant (U127527198).
Topics: Aged; Female; Humans; Male; Middle Aged; Air Pollutants; Air Pollution; Colorectal Neoplasms; DNA Methylation; Environmental Exposure; Epigenesis, Genetic; Epigenomics; Gene-Environment Interaction; Incidence; Mendelian Randomization Analysis; Prospective Studies; Risk Factors
PubMed: 38631091
DOI: 10.1016/j.ebiom.2024.105126 -
Iranian Journal of Basic Medical... 2024Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits... (Review)
Review
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits and has anti-inflammatory, anti-oxidant, and anti-MetS properties. This study aims to systematically review the effects of apigenin against MetS and the relevant molecular and cellular mechanisms of action, pharmacokinetics features, and potential structure-activity relationship. Electronic databases including Scopus, PubMed, Science Direct and Cochrane Library were searched for in vivo, and in vitro, and human studies with the following keywords: "apigenin" and "metabolic syndrome or insulin resistance syndrome", "fatty liver", "hypertension or blood pressure", "diabetes or blood glucose", "dyslipidemia", "heart or cardiovascular " and "obesity" in title/abstract. Data were collected from 2000 until 2021 (up to April). Only papers published in the English language were included. Forty-six full-text articles out of 1016 retrieved papers were reviewed and underwent quality assessment by investigators. Anti-obesity activity of apigenin is mainly through attenuating adipocyte differentiation by suppressing the mitotic clonal expansion and the adipogenesis-related factors. Its anti-diabetic effects can be exerted through inhibition of protein tyrosine phosphatase1B expression, maintaining the activity of anti-oxidant enzymes, reducing intracellular ROS production, cellular DNA damage, protein carbonylation, and attenuating β-cell apoptosis. Moreover, apigenin could attenuate dyslipidemia and subsequent atherosclerotic conditions through down-regulating sterol regulatory element-binding proteins (SREBP)-1c, SREBP-2, stearyl-CoA desaturase-1, and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Apigenin as a dietary bioactive compound would be a promising candidate for improving MetS and its components.
PubMed: 38629096
DOI: 10.22038/IJBMS.2024.71539.15558 -
Gynecologic and Obstetric Investigation Apr 2024DNA methylation plays an important role in the carcinogenesis, progression, and prognosis of various human cancers. RASSF1A, BRCA1, APC, and p16 are the frequently...
INTRODUCTION
DNA methylation plays an important role in the carcinogenesis, progression, and prognosis of various human cancers. RASSF1A, BRCA1, APC, and p16 are the frequently methylated genes among patients with ovarian cancer. Therefore, our study aimed to better determine the prognostic and cancer characteristics effects of RASSF1A, BRCA1, APC, and p16 promoter methylation in ovarian cancer patients.
METHODS
Databases such as PubMed, Web of Science, EMBASE, CNKI, and WanFang were searched for published studies up to March 4, 2024. The outcomes are shown as OR and HR with their 95% CIs. Then, the random or fixed-effect model was performed to evaluate the effect sizes.
RESULTS
Finally, 27 articles were included in this meta-analysis. No significant relationships were observed between RASSF1A, BRCA1, and APC promoter methylation and the clinical prognostic (including overall survival and progression-free survival) and cancer characteristics (including ascites, lymph node metastasis, and pelvic peritoneal metastasis) in ovarian cancer. p16 promoter methylation was significantly related to poor progression-free survival (PFS) (HR = 1.52, 95% CI = 1.14-2.04) and overall survival (OS) (HR = 1.39, 95% CI = 1.06, to 1.83) in univariate and poor PFS in multivariate Cox regression models (HR = 1.42, 95% CI = 1.05-1.92). Besides, our results indicated that the clinical stage was associated with inferior OS while there was no significant association between tumor grade and OS.
CONCLUSION
RASSF1A, BRCA1, and APC promoter methylation were not significantly associated with clinical prognostic and cancer characteristics. p16 may be a useful biomarker for predicting PFS in ovarian cancer. Furthermore, the clinical stage was significantly associated with OS. In further research, more prospective and multicenter validation studies remain needed.
PubMed: 38615670
DOI: 10.1159/000538673 -
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 -
Neurosurgical Review Apr 2024Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after... (Review)
Review
Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.
Topics: Humans; Subarachnoid Hemorrhage; DNA Methylation; Cerebral Infarction; Brain Ischemia; Biomarkers; Vasospasm, Intracranial; Cadherin Related Proteins
PubMed: 38594575
DOI: 10.1007/s10143-024-02381-5 -
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 -
Psychiatry Research May 2024We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating... (Meta-Analysis)
Meta-Analysis Review
We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.
Topics: Humans; Hallucinogens; Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine; Lysergic Acid Diethylamide; Mental Disorders; Obsessive-Compulsive Disorder
PubMed: 38574699
DOI: 10.1016/j.psychres.2024.115886 -
F&S Reviews Jan 2024To assess the current literature evaluating the epigenetics of endometriosis in humans.
OBJECTIVE
To assess the current literature evaluating the epigenetics of endometriosis in humans.
EVIDENCE REVIEW
A systematic review was conducted in accordance with the PRISMA guidelines within PubMed, EBSCOhost, Cochrane Library, Embase, Scopus, and Web of Science Core Collection. A comprehensive search strategy was developed by a data informationist. Observational and interventional studies assessing epigenetics in humans published in English up to January 15th, 2023, were included. Two reviewers independently screened studies evaluating the role of epigenetics in endometriosis. The risk of bias was assessed using Cochrane RoB 2.0 tool and the Newcastle-Ottawa scale. Extracted data were analyzed descriptively.
RESULTS
We identified 18.639 studies, of which 57 were included, comprising 1.623 patients with endometriosis and 1.243 controls. Among the 57 studies included, 50 (88%) were case-control studies, and 7 (12%) were cross-sectional. Fifty-nine percent of the studies were Asian, 25% were from America, 14% were European, and 2% were from Africa. Acetylation and methylation were the two main key histone modifications that were centered in this review. Accordingly, we classified the studies as those focusing on genome-wide methylation and those on histone acetylation. Several studies identified an association between endometriosis and hypermethylated genes, including the PGR-B, SF-1, and RASSF1A. The genes HOXA10, COX-2, IL-12B, and GATA6 were found to be hypomethylated in endometriotic tissue by several studies. In regards to histone modification, multiple studies reported that the acetylation levels of histones H3 and H4 affect multiple genes associated with endometriosis. In addition, HDAC2 was found to be elevated in endometriosis patients in two studies.
CONCLUSION
Several studies reported a significant difference between specific genes' methylation levels in endometrial biopsies and normal tissue, which suggests that DNA methylation may play an important role in the modulation of the genotype in endometriotic tissue. Acetylation and methylation are the two key histone modifications leading to differential gene expression in endometriotic tissues. The alterations in gene expression reported by the 57 studies can have direct implications on cell cycle growth, cell cycle arrest, and apoptosis and, therefore, might play a key role in the pathogenesis of endometriosis. This review offers insight that histone modifications need further research to evaluate their role as potential biomarkers and treatment targets for endometriosis. Although several key similarities were reported, there were some disagreements among the results, which might be attributable to the heterogeneity between studies. Further research with a more robust standardization is needed to validate the epigenetic changes in endometriosis.
PubMed: 38524912
DOI: 10.1016/j.xfnr.2024.01.003 -
BMC Neurology Mar 2024MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT...
BACKGROUND
MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS
To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS
We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSION
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Topics: Humans; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Prognosis; Tumor Suppressor Proteins
PubMed: 38521933
DOI: 10.1186/s12883-024-03605-3 -
Journal of Comparative Effectiveness... May 2024In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of... (Comparative Study)
Comparative Study Review
Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.
In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.
Topics: Humans; Hydromorphone; Fentanyl; Analgesics, Opioid; Acute Pain; Randomized Controlled Trials as Topic; Vomiting; Nausea; Administration, Intravenous; Respiratory Insufficiency; Pain Management; Quinuclidines; Spiro Compounds; Thiophenes
PubMed: 38497192
DOI: 10.57264/cer-2023-0041