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Clinical and Experimental Allergy :... Mar 2023The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA).
DESIGN
A systematic review of the literature and meta-analysis were carried out within several databases. However, the risk of bias in the included articles was not evaluated.
DATA SOURCES
PubMed, Cochrane Database of Systematic Reviews, and Web of Science were used to search up to July 2022.
ELIGIBILITY CRITERIA
We included targeted and epigenome-wide association studies (EWASs) that assessed DNA methylome alterations in association with FA in adult or paediatric populations.
RESULTS
Among 366 publications, only 16 were retained, which were mainly focused on FA in children. Seven candidate gene-targeted studies found associations in Th1/Th2 imbalance (IL4, IL5, IL10, INFG, IL2 and IL12B genes), regulatory T cell function (FOXP3 gene), Toll-like receptors pathway (TLR2, CD14 genes) and digestive barrier integrity (FLG gene). Nine EWAS assessed the association with peanut allergy (n = 3), cow's milk allergy (n = 2) or various food allergens (n = 4). They highlighted 11 differentially methylated loci in at least two studies (RPS6KA2, CAMTA1, CTBP2, RYR2, TRAPPC9, DOCK1, GALNTL4, HDAC4, UMODL1, ZAK and TNS3 genes). Among them, CAMTA1 and RPS6KA2, and CTBP2 are involved in regulatory T cell function and Th2 cell differentiation, respectively. Gene-functional analysis revealed two enriched gene clusters involved in immune responses and protein phosphorylation. ChIP-X Enrichment Analysis 3 showed eight significant transcription factors (RXRA, ZBTB7A, ESR1, TCF3, MYOD1, CTCF, GATA3 and CBX2). Ingenuity Pathway Analysis identified canonical pathways involved, among other, in B cell development, pathogen-induced cytokine storm signalling pathway and dendritic cell maturation.
CONCLUSION
This review highlights the involvement of epigenomic alterations of loci in Th1/Th2 and regulatory T cell differentiation in both candidate gene studies and EWAS. These alterations provide a better insight into the mechanistic aspects in FA pathogenesis and may guide the development of epigenome-based biomarkers for FA.
Topics: Female; Animals; Cattle; Epigenome; Cell Line, Tumor; Transcription Factors; DNA-Binding Proteins; Food Hypersensitivity; Milk Hypersensitivity
PubMed: 36756739
DOI: 10.1111/cea.14277 -
European Journal of Medicinal Chemistry Nov 2018In this review, we describe a detailed investigation about the structural variations and relative activity of 1,8-naphthalimide based intercalators and anticancer... (Review)
Review
In this review, we describe a detailed investigation about the structural variations and relative activity of 1,8-naphthalimide based intercalators and anticancer agents. The 1,8-naphthalimides binds to the DNA via intercalation, and exert their antitumor activities through Topoisomerase I/II inhibition, photoinduced DNA damage or related mechanism. Here, our discussion focused on works published over the last ten years (2007-2017) related to therapeutic applications, in the order of cancer treatment followed by other properties of 1,8-naphthalimides. In preparing for this review, we considered that several seminal reviews have appeared over the last fifteen years and focused on closely related subjects, however, none of them is exhaustive.
Topics: Antineoplastic Agents; Cell Proliferation; DNA Damage; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; DNA, Neoplasm; Humans; Intercalating Agents; Naphthalimides; Neoplasms; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors
PubMed: 30312931
DOI: 10.1016/j.ejmech.2018.09.055 -
Developmental Neurobiology Mar 2021Ash1l potentially contributes to neurodevelopmental diseases. Although specific Ash1l mutations are rare, they have led to informative studies in animal models that may... (Review)
Review
Ash1l potentially contributes to neurodevelopmental diseases. Although specific Ash1l mutations are rare, they have led to informative studies in animal models that may bring therapeutic advances. Ash1l is highly expressed in the brain and correlates with the neuropathology of Tourette syndrome (TS), autism spectrum disorder, and intellectual disability during development, implicating shared epigenetic factors and overlapping neuropathological mechanisms. Functional convergence of Ash1l generated several significant signaling pathways: chromatin remodeling and transcriptional regulation, protein synthesis and cellular metabolism, and synapse development and function. Here, we systematically review the literature on Ash1l, including its discovery, expression, function, regulation, implication in the nervous system, signaling pathway, mutations, and putative involvement in TS and other neurodevelopmental traits. Such findings highlight Ash1l pleiotropy and the necessity of transcending a single gene to complicated mechanisms of network convergence underlying these diseases. With the progress in functional genomic analysis (highlighted in this review), and although the importance and necessity of Ash1l becomes increasingly apparent in the medical field, further research is required to discover the precise function and molecular regulatory mechanisms related to Ash1l. Thus, a new perspective is proposed for basic scientific research and clinical interventions for cross-disorder diseases.
Topics: Animals; Autism Spectrum Disorder; DNA-Binding Proteins; Intellectual Disability; Neurodevelopmental Disorders; Tourette Syndrome
PubMed: 33258273
DOI: 10.1002/dneu.22795 -
Biochemistry. Biokhimiia Jan 2024Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the... (Review)
Review
Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and an overview of the results of modelling FUS-proteinopathy in animals.
Topics: Animals; Humans; Amyotrophic Lateral Sclerosis; RNA-Binding Protein FUS; Motor Neurons; Cytoplasm; Mutation; Disease Models, Animal
PubMed: 38621743
DOI: 10.1134/S0006297924140037 -
Asian Pacific Journal of Cancer... 2016Breast cancer risk assessment has developed during years and evaluation of genetic factor affecting risk of breast cancer is an important component of this risk... (Meta-Analysis)
Meta-Analysis Review
Breast cancer risk assessment has developed during years and evaluation of genetic factor affecting risk of breast cancer is an important component of this risk assessment. The aim of this meta-analysis was to investigate the role of XRCC1 polymorphisms (Arg194Trp, Arg280His and Arg399Gln) for risk of breast cancer among different population and categories of menopausal status. PubMed, Medline, Web of Science, and PubMed Central were systematically searched to identify studies evaluating association between breast cancer and XRCC1 gene polymorphisms (Arg194Trp, Arg280His and Arg399Gln). Two authors independently extracted required information. Odds Ratios were pooled for four genetic inheritance models using both fixed and the DerSimonian and Laird random-effect models. Egger's test and contour-enhanced funnel plot were used to evaluate publication bias and small study effect. Additional subgroup analysis was performed for menopausal status, ethnicity, and source of controls. After evaluation and applying inclusion criteria on extracted studies, fifty three studies were included in this meta-analysis. For polymorphisms of Arg194Trp and Arg280His, no significant association was observed in all genetic models. Arg194Trp had a protective effect in post-menopausal status only in homozygote model (OR=0.57 [0.37-0.88]). Arg399Gln showed significant association with breast cancer in homozygote (OR=1.21 [1.10-1.34]), dominant (OR=1.09 [1.03-1.15]) and recessive (OR=1.21 [1.09-1.35]) models. Arg399Gln was associated with higher risk in post-menopausal status for homozygote and heterozygote models. Our findings suggest that XRCC1 gene polymorphisms modify breast cancer risk in different populations and different categories of menopausal status.
Topics: Breast Neoplasms; Case-Control Studies; DNA-Binding Proteins; Female; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Prognosis; Risk Factors; X-ray Repair Cross Complementing Protein 1
PubMed: 27165246
DOI: 10.7314/apjcp.2016.17.s3.323 -
Oncotarget Dec 2016Recent studies explored XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian cancer (OC) risk. However, the association between these two single nucleotide... (Meta-Analysis)
Meta-Analysis Review
Recent studies explored XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian cancer (OC) risk. However, the association between these two single nucleotide polymorphisms and OC risk remains conflicting. Thus, we conducted a comprehensive systematic review and meta-analysis to investigate the association. We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. 15 case-control studies published in 11 papers including 4,757 cases and 8,431 controls were included in this meta-analysis. No associations were obtained between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and OC risk. Stratification analyses of Hardy-Weinberg equilibrium status indicated that rs3218536 polymorphism was associated with the decreased risk of OC when in analysis of combined HWE positive studies. In conclusion, this meta-analysis indicates that XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms may not be associated with the risk of OC.
Topics: Case-Control Studies; DNA-Binding Proteins; Female; Humans; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein
PubMed: 27863412
DOI: 10.18632/oncotarget.13361 -
Neurotoxicology Dec 2020Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological...
Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients. However, a body of epidemiological, clinical and experimental evidences suggest that lead (Pb), more than other metals, could actually play a major role in the onset and progression of ALS. Here, to clarify the nature of the association and the causative role of Pb in ALS, we comprehensively reviewed the scientific literature of the last decade with objective database searches and the methods typically adopted in systematic reviews, critically analysing and summarising the various scientifically sound evidence on the relationship between ALS and Pb. From these tasks, we noted a number of multidisciplinary associations between ALS and Pb, and specifically the importance of occupational exposure to Pb in ALS development and/or progression. We also report the possible involvement of TAR DNA binding protein (TDP-43)-based molecular mechanism in Pb-mediated ALS, although these data rely on a single study, which included both in vitro experiments and an animal model, and are therefore still preliminary. Finally, we briefly examined whether this knowledge could inspire new targeted therapies and policies in the fight against ALS.
Topics: Amyotrophic Lateral Sclerosis; Animals; Central Nervous System; DNA-Binding Proteins; Disease Progression; Environmental Exposure; Environmental Pollutants; Gene-Environment Interaction; Humans; Lead; Lead Poisoning, Nervous System; Protein Aggregates; Protein Aggregation, Pathological; Risk Assessment; Risk Factors
PubMed: 32941938
DOI: 10.1016/j.neuro.2020.09.003 -
The Lancet. Microbe Feb 2024Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.
METHODS
We screened public databases for articles published from database inception until Oct 31, 2022. Eligible studies performed sequencing of at least mmpR5 and atpE on clinically sourced M tuberculosis isolates and measured bedaquiline minimum inhibitory concentrations (MICs). A bias risk scoring tool was used to identify bias. Individual genetic mutations and corresponding MICs were aggregated, and odds ratios calculated to determine association of mutations with resistance. Machine-based learning methods were used to define test characteristics of parsimonious sets of diagnostic RAVs, and mmpR5 mutations were mapped to the protein structure to highlight mechanisms of resistance. This study was registered in the PROSPERO database (CRD42022346547).
FINDINGS
18 eligible studies were identified, comprising 975 M tuberculosis isolates containing at least one potential RAV (mutation in mmpR5, atpE, atpB, or pepQ), with 201 (20·6%) showing phenotypic bedaquiline resistance. 84 (29·5%) of 285 resistant isolates had no candidate gene mutation. Sensitivity and positive predictive value of taking an any mutation approach was 69% and 14%, respectively. 13 mutations, all in mmpR5, had a significant association with a resistant MIC (adjusted p<0·05). Gradient-boosted machine classifier models for predicting intermediate or resistant and resistant phenotypes both had receiver operator characteristic c statistic of 0·73 (95% CI 0·70-0·76). Frameshift mutations clustered in the α1 helix DNA-binding domain, and substitutions in the α2 and α3 helix hinge region and in the α4 helix-binding domain.
INTERPRETATION
Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified, some mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics. This study was limited by selective sampling in contributing studies and only considering single genetic loci as causative of resistance.
FUNDING
Francis Crick Institute and National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Topics: United States; Humans; Antitubercular Agents; Diarylquinolines; Tuberculosis; Mycobacterium tuberculosis; Genomics
PubMed: 38215766
DOI: 10.1016/S2666-5247(23)00317-8 -
Epigenomics Jul 2017Evidence points to the role of DNA methylation in ulcerative colitis (UC)-associated cancer (UCC), the most serious complication of ulcerative colitis. A better... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence points to the role of DNA methylation in ulcerative colitis (UC)-associated cancer (UCC), the most serious complication of ulcerative colitis. A better understanding of the etiology of UCC may facilitate the development of new therapeutic targets and help to identify biomarkers of the disease risk.
METHODS
A search was performed in three databases following PRISMA protocol. DNA methylation in UCC was compared with sporadic colorectal cancer (SCRC), and individual genes differently methylated in UCC identified.
RESULTS
While there were some similarities in the methylation patterns of UCC compared with SCRC, generally lower levels of hypermethylation in promoter regions of individual genes was evident in UCC. Certain individual genes are, however, highly methylated in colitis-associated cancer: RUNX3, MINT1, MYOD and p16 exon1 and the promoter regions of EYA4 and ESR.
CONCLUSION
Patterns of DNA methylation differ between UCC and SCRC. Seven genes appear to be promising putative biomarkers.
Topics: Adaptor Proteins, Signal Transducing; Biomarkers, Tumor; Colitis, Ulcerative; Colorectal Neoplasms; Core Binding Factor Alpha 3 Subunit; DNA Methylation; Female; Humans; Male; MyoD Protein; Nerve Tissue Proteins; Trans-Activators
PubMed: 28621161
DOI: 10.2217/epi-2017-0025 -
Journal of Diabetes Research 2017The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating... (Meta-Analysis)
Meta-Analysis Review
The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating nesfatin-1 levels and type 2 diabetes, the conclusions are contradictory. We aimed to probe the relationship between circulating nesfatin-1 levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2 diabetes patients and 294 control subjects were included. Although there was no obvious difference in circulating nesfatin-1 levels between patients with type 2 diabetes and the control group (MD = -0.04; 95% CI = -0.32 to -0.23), subgroup analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1 levels in type 2 diabetes patients receiving antidiabetic treatment (MD = -0.26; 95% CI = -0.33 to -0.20). In conclusion, the analysis supports a relationship between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2 diabetes patients receiving antidiabetic treatment showed lower circulating nesfatin-1 levels.
Topics: Biomarkers; Calcium-Binding Proteins; DNA-Binding Proteins; Diabetes Mellitus, Type 2; Disease Progression; Down-Regulation; Humans; Hypoglycemic Agents; Nerve Tissue Proteins; Nucleobindins; Reproducibility of Results; Up-Regulation
PubMed: 29445751
DOI: 10.1155/2017/7687098