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Nutrition, Metabolism, and... Jul 2016New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition... (Review)
Review
BACKGROUND
New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences.
AIM
To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR).
METHOD AND RESULTS
Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies.
CONCLUSIONS AND RELEVANCE
Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.
Topics: Acetylation; Biomarkers; Blood Glucose; Chromatin Assembly and Disassembly; DNA Methylation; Diabetes Mellitus, Type 2; Epigenesis, Genetic; Female; Gene Expression Regulation; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Histones; Humans; Insulin; Insulin Resistance; Male; Phenotype; Risk Factors
PubMed: 27146363
DOI: 10.1016/j.numecd.2016.04.002 -
Journal of Human Hypertension Oct 2019Epigenetic mechanisms might play a role in the pathophysiology of hypertension, a major risk factor for cardiovascular disease and renal failure. We aimed to...
Epigenetic mechanisms might play a role in the pathophysiology of hypertension, a major risk factor for cardiovascular disease and renal failure. We aimed to systematically review studies investigating the association between epigenetic marks (global, candidate-gene or genome-wide methylation of DNA, and histone modifications) and blood pressure or hypertension. Five bibliographic databases were searched until the 7th of December 2018. Of 2984 identified references, 26 articles based on 25 unique studies met our inclusion criteria, which involved a total of 28,382 participants. The five studies that assessed global DNA methylation generally found lower methylation levels with higher systolic blood pressure, diastolic blood pressure, and/or presence of hypertension. Eighteen candidate-gene studies reported, in total, 16 differentially methylated genes, including renin-angiotensin-system-related genes (ACE promoter and AGTR1) and genes involved in sodium homeostasis and extracellular fluid volume maintenance system (NET promoter, SCNN1A, and ADD1). Between the three identified epigenome-wide association studies (EWAS), lower methylation levels of SULF1, EHMT2, and SKOR2 were found in hypertensive patients as compared with normotensive subjects, and lower methylation levels of PHGDH, SLC7A11, and TSPAN2 were associated with higher systolic and diastolic blood pressure. In summary, the most convincing evidence has been reported from candidate-gene studies, which show reproducible epigenetic changes in the interconnected renin-angiotensin and inflammatory systems. Our study highlights gaps in the literature on the role of histone modifications in blood pressure and the need to conduct high-quality studies, in particular, hypothesis-generating studies that may help to elucidate new molecular mechanisms.
Topics: Blood Pressure; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Female; Genetic Association Studies; Genetic Predisposition to Disease; Histones; Humans; Hypertension; Male; Phenotype; Risk Factors
PubMed: 31346255
DOI: 10.1038/s41371-019-0218-7 -
Pharmacological Research Feb 2022Antipsychotics represent the mainstay of schizophrenia pharmacological therapy, and their role has been expanded in the last years to mood disorders treatment. Although...
Antipsychotics represent the mainstay of schizophrenia pharmacological therapy, and their role has been expanded in the last years to mood disorders treatment. Although introduced in 1952, many years of research were required before an accurate picture of how antipsychotics work began to emerge. Despite the well-recognized characterization of antipsychotics in typical and atypical based on their liability to induce motor adverse events, their main action at dopamine D2R to elicit the "anti-psychotic" effect, as well as the multimodal action at other classes of receptors, their effects on intracellular mechanisms starting with receptor occupancy is still not completely understood. Significant lines of evidence converge on the impact of these compounds on multiple molecular signaling pathways implicated in the regulation of early genes and growth factors, dendritic spine shape, brain inflammation, and immune response, tuning overall the function and architecture of the synapse. Here we present, based on PRISMA approach, a comprehensive and systematic review of the above mechanisms under a translational perspective to disentangle those intracellular actions and signaling that may underline clinically relevant effects and represent potential targets for further innovative strategies in antipsychotic therapy.
Topics: Animals; Antipsychotic Agents; Brain; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Gene Expression Regulation; Genes, Immediate-Early; Humans; Neuronal Plasticity; Neuroprotective Agents; Neurotransmitter Transport Proteins
PubMed: 35026403
DOI: 10.1016/j.phrs.2022.106078 -
Life Sciences Jan 2016Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food... (Review)
Review
Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases.
Topics: Animals; Carcinogens, Environmental; Cardiovascular System; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Hormones; Humans; Nervous System; Obesity; Reproduction
PubMed: 26497928
DOI: 10.1016/j.lfs.2015.10.022 -
Reviews on Environmental Health Dec 2023Due to the widespread use and environmental pollution of estrogenic chemicals, the need for screening tests to detect these compounds is felt more than ever. These... (Review)
Review
Due to the widespread use and environmental pollution of estrogenic chemicals, the need for screening tests to detect these compounds is felt more than ever. These compounds lead to cell proliferation. Therefore, studies used cell proliferation to evaluate estrogenic compounds was studied in this systematic review. This systematic review was performed with the keywords; DNA proliferation, cell proliferation, estrogenic component, estrogen, food, bioassay, screening, and detection. After initial screening and full text quality assessment, 16 manuscripts were selected and data were extracted. Four cell lines, MCF-7, MDA-MB-231, Ishikawa, and T47D cells were used in the studies. MCF-7 was more sensitive to estrogenic compounds than other lines. Most of the samples studied were plant compounds and mycotoxins and substances that migrate from packaging to food. This screening test is valid and has similar results as others.
Topics: Estrogens; Cell Proliferation; Biological Assay
PubMed: 35934880
DOI: 10.1515/reveh-2022-0035 -
Frontiers in Genetics 2023Histone variants, which generally differ in few amino acid residues, can replace core histones (H1, H2A, H2B, and H3) to confer specific structural and functional...
Histone variants, which generally differ in few amino acid residues, can replace core histones (H1, H2A, H2B, and H3) to confer specific structural and functional features to regulate cellular functions. In addition to their role in DNA packaging, histones modulate key processes such as gene expression regulation and chromosome segregation, which are frequently dysregulated in cancer cells. During the years, histones variants have gained significant attention as gatekeepers of chromosome stability, raising interest in understanding how structural and functional alterations can contribute to tumourigenesis. Beside the well-established role of the histone H3 variant CENP-A in centromere specification and maintenance, a growing body of literature has described mutations, aberrant expression patterns and post-translational modifications of a variety of histone variants in several cancers, also coining the term "oncohistones." At the molecular level, mechanistic studies have been dissecting the biological mechanisms behind histones and missegregation events, with the potential to uncover novel clinically-relevant targets. In this review, we focus on the current understanding and highlight knowledge gaps of the contribution of histone variants to aneuploidy, and we have compiled a database (HistoPloidyDB) of histone gene alterations linked to aneuploidy in cancers of the The Cancer Genome Atlas project.
PubMed: 38075697
DOI: 10.3389/fgene.2023.1290903 -
International Journal of Molecular... May 2022Coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe health crisis,... (Review)
Review
Coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe health crisis, causing extraordinary economic disruption worldwide. SARS-CoV-2 is a single-stranded RNA-enveloped virus. The process of viral replication and particle packaging is finished in host cells. Viral proteins, including both structural and nonstructural proteins, play important roles in the viral life cycle, which also provides the targets of treatment. Therefore, a better understanding of the structural function of virus proteins is crucial to speed up the development of vaccines and therapeutic strategies. Currently, the structure and function of proteins encoded by the SARS-CoV-2 genome are reviewed by several studies. However, most of them are based on the analysis of SARS-CoV-1 particles, lacking a systematic review update for SARS-CoV-2. Here, we specifically focus on the structure and function of proteins encoded by SARS-CoV-2. Viral proteins that contribute to COVID-19 infection and disease pathogenesis are reviewed according to the most recent research findings. The structure-function correlation of viral proteins provides a fundamental rationale for vaccine development and targeted therapy. Then, current antiviral vaccines are updated, such as inactive viral vaccines and protein-based vaccines and DNA, mRNA, and circular RNA vaccines. A summary of other therapeutic options is also reviewed, including monoclonal antibodies such as a cross-neutralizer antibody, a constructed cobinding antibody, a dual functional monoclonal antibody, an antibody cocktail, and an engineered bispecific antibody, as well as peptide-based inhibitors, chemical compounds, and clustered regularly interspaced short palindromic repeats (CRISPR) exploration. Overall, viral proteins and their functions provide the basis for targeted therapy and vaccine development.
Topics: Antibodies, Viral; Antiviral Agents; COVID-19; Humans; SARS-CoV-2; Viral Proteins; Viral Vaccines
PubMed: 35682761
DOI: 10.3390/ijms23116083 -
Pathologica Dec 2012Colorectal carcinoma (CRC) is the second most frequent malignant disease in developed countries. Many aetiological factors have been reported in CRC development... (Review)
Review
Colorectal carcinoma (CRC) is the second most frequent malignant disease in developed countries. Many aetiological factors have been reported in CRC development including genetic or non-genetic (environmental) elements. Independently of these, three groups of alterations have been implicated: 1) chromosomal instability (CIN); 2) microsatellite instability (MSI); 3) CpG island methylator phenotype (CIMP). A different multistep association between these alterations contributes to determine three distinct developmental pathways: traditional, alternative and serrated. Each genotypic CRC assessment is associated with specific morphologic or clinical features. Pathologists have to consider the morphologic and clinical features of each CRC when study tumours with molecular tests. Chromatin remodelling is extremely dynamic and depends on several DNA-based processes, such as transcription, DNA repair and replication. The recent results with whole genome sequencing in a vast array of cancers have provided a catalogue of genetic lesions in chromatin modifiers that were previously unappreciated. It has revealed surprising facts about mutations in several SWI/ SNF complex members in many malignancies including CRC. The loss of INI1 expression is detected at a low rate in CRC and may be associated with differentiation grade and survival. Accumulating evidence suggests a critical role of the epithelial mesenchymal transition (EMT) in cancer progression. Some results support the existence of crosstalk between EMT and epigenetic modifications in the MSI-CRC group. We have summarized the role of genetic/epigenetic changes in the origin of the multiple CRC pathway, taking into account current knowledge of pathogenesis and feasibility of designing novel therapeutic approaches.
Topics: Carcinoma; Chromatin Assembly and Disassembly; Colon; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Pathology; Physician's Role
PubMed: 23547429
DOI: No ID Found -
Epigenetics & Chromatin Nov 2020ATP-dependent chromatin remodeling by histone-modifying enzymes and chromatin remodeling complexes is crucial for maintaining chromatin organization and facilitating...
ATP-dependent chromatin remodeling by histone-modifying enzymes and chromatin remodeling complexes is crucial for maintaining chromatin organization and facilitating gene transcription. In the SWI/SNF family of ATP-dependent chromatin remodelers, distinct complexes such as BAF, PBAF, GBAF, esBAF and npBAF/nBAF are of particular interest regarding their implications in cellular differentiation and development, as well as in various diseases. The recently identified BAF subcomplex GBAF is no exception to this, and information is emerging linking this complex and its components to crucial events in mammalian development. Furthermore, given the essential nature of many of its subunits in maintaining effective chromatin remodeling function, it comes as no surprise that aberrant expression of GBAF complex components is associated with disease development, including neurodevelopmental disorders and numerous malignancies. It becomes clear that building upon our knowledge of GBAF and BAF complex function will be essential for advancements in both mammalian reproductive applications and the development of more effective therapeutic interventions and strategies. Here, we review the roles of the SWI/SNF chromatin remodeling subcomplex GBAF and its subunits in mammalian development and disease.
Topics: Animals; Chromatin Assembly and Disassembly; Chromosomal Proteins, Non-Histone; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Humans; Transcription Factors
PubMed: 33143733
DOI: 10.1186/s13072-020-00370-8