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Evangelina R, Ganesan S, George M. The Epigenetic Landscape: From Molecular Mechanisms to Biological Aging. Rejuvenation Res 2025. [PMID: 40094262 DOI: 10.1089/rej.2024.0102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025] Open
Abstract
Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the deoxyribonucleic acid (DNA) sequence, plays a pivotal role in cellular function, development, and aging. This review explores key epigenetic mechanisms, including DNA methylation (DNAm), histone modifications, chromatin remodeling, RNA-based regulation, and long-distance chromosomal interactions. These modifications contribute to cellular differentiation and function, mediating the dynamic interplay between the genome and environmental factors. Epigenetic clocks, biomarkers based on DNAm patterns, have emerged as powerful tools to measure biological age and predict health span. This article highlights the evolution of epigenetic clocks, from first-generation models such as Horvath's multi-tissue clock to advanced second- and third-generation clocks such as DNAGrimAge and DunedinPACE, which incorporate biological parameters and clinical biomarkers for precise age estimation. Moreover, the role of epigenetics in aging and age-related diseases is discussed, emphasizing its impact on genomic stability, transcriptional regulation, and cellular senescence. Epigenetic dysregulation is implicated in cancer, genetic disorders, and neurodegenerative diseases, making it a promising target for therapeutic interventions. The reversibility of epigenetic modifications offers hope for mitigating age acceleration and enhancing health span through lifestyle changes and pharmacological approaches.
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Affiliation(s)
- Rachel Evangelina
- Centre for Clinical Pharmacology, SRM Medical College, Hospital and Research Centre, Kattankulathur, Tamil Nadu, India
| | - Subhashree Ganesan
- Centre for Clinical Pharmacology, SRM Medical College, Hospital and Research Centre, Kattankulathur, Tamil Nadu, India
| | - Melvin George
- Centre for Clinical Pharmacology, SRM Medical College, Hospital and Research Centre, Kattankulathur, Tamil Nadu, India
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2
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Izadi M, Sadri N, Abdi A, Serajian S, Jalalei D, Tahmasebi S. Epigenetic biomarkers in aging and longevity: Current and future application. Life Sci 2024; 351:122842. [PMID: 38879158 DOI: 10.1016/j.lfs.2024.122842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 06/06/2024] [Accepted: 06/12/2024] [Indexed: 06/20/2024]
Abstract
The aging process has been one of the most necessary research fields in the current century, and knowing different theories of aging and the role of different genetic, epigenetic, molecular, and environmental modulating factors in increasing the knowledge of aging mechanisms and developing appropriate diagnostic, therapeutic, and preventive ways would be helpful. One of the most conserved signs of aging is epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, noncoding RNAs, and extracellular RNAs. Numerous biological processes and hallmarks are vital in aging development, but epigenomic alterations are especially notable because of their importance in gene regulation and cellular identity. The mounting evidence points to a possible interaction between age-related epigenomic alterations and other aging hallmarks, like genome instability. To extend a healthy lifespan and possibly reverse some facets of aging and aging-related diseases, it will be crucial to comprehend global and locus-specific epigenomic modifications and recognize corresponding regulators of health and longevity. In the current study, we will aim to discuss the role of epigenomic mechanisms in aging and the most recent developments in epigenetic diagnostic biomarkers, which have the potential to focus efforts on reversing the destructive signs of aging and extending the lifespan.
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Affiliation(s)
- Mehran Izadi
- Department of Infectious and Tropical Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran; Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
| | - Nariman Sadri
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran; Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran; School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhossein Abdi
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran; Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran; Royan Institute for Stem Cell Biology and Technology, Tehran, Iran
| | - Sahar Serajian
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran; Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran; Royan Institute for Stem Cell Biology and Technology, Tehran, Iran
| | - Dorsa Jalalei
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran; Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran; School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Safa Tahmasebi
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran; Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran; Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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3
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Carballo-Perich L, Puigoriol-Illamola D, Bashir S, Terceño M, Silva Y, Gubern-Mérida C, Serena J. Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis. Int J Mol Sci 2022; 23:5149. [PMID: 35563540 PMCID: PMC9101730 DOI: 10.3390/ijms23095149] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/29/2022] [Accepted: 05/02/2022] [Indexed: 12/24/2022] Open
Abstract
Atheromatous disease is the first cause of death and dependency in developed countries and carotid artery atherosclerosis is one of the main causes of severe ischaemic strokes. Current management strategies are mainly based on the degree of stenosis and patient selection has limited accuracy. This information could be complemented by the identification of biomarkers of plaque vulnerability, which would permit patients at greater and lesser risk of stroke to be distinguished, thus enabling a better selection of patients for surgical or intensive medical treatment. Although several circulating protein-based biomarkers with significance for both the diagnosis of carotid artery disease and its prognosis have been identified, at present, none have been clinically implemented. This review focuses especially on the most relevant clinical parameters to take into account in routine clinical practice and summarises the most up-to-date data on epigenetic biomarkers of carotid atherosclerosis and plaque vulnerability.
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Affiliation(s)
- Laia Carballo-Perich
- Cerebrovascular Pathology Research Group, Girona Biomedical Research Institute (IDIBGI), RICORS-ICTUS, Parc Hospitalari Martí I Julià, Edifici M2, 17190 Salt, Spain; (L.C.-P.); (D.P.-I.)
| | - Dolors Puigoriol-Illamola
- Cerebrovascular Pathology Research Group, Girona Biomedical Research Institute (IDIBGI), RICORS-ICTUS, Parc Hospitalari Martí I Julià, Edifici M2, 17190 Salt, Spain; (L.C.-P.); (D.P.-I.)
| | - Saima Bashir
- Cerebrovascular Pathology Research Group, Stroke Unit, Department of Neurology, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, RICORS-ICTUS, Av. França s/n (7a Planta), 17007 Girona, Spain; (S.B.); (M.T.); (J.S.)
| | - Mikel Terceño
- Cerebrovascular Pathology Research Group, Stroke Unit, Department of Neurology, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, RICORS-ICTUS, Av. França s/n (7a Planta), 17007 Girona, Spain; (S.B.); (M.T.); (J.S.)
| | - Yolanda Silva
- Cerebrovascular Pathology Research Group, Stroke Unit, Department of Neurology, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, RICORS-ICTUS, Av. França s/n (7a Planta), 17007 Girona, Spain; (S.B.); (M.T.); (J.S.)
| | - Carme Gubern-Mérida
- Cerebrovascular Pathology Research Group, Girona Biomedical Research Institute (IDIBGI), RICORS-ICTUS, Parc Hospitalari Martí I Julià, Edifici M2, 17190 Salt, Spain; (L.C.-P.); (D.P.-I.)
| | - Joaquín Serena
- Cerebrovascular Pathology Research Group, Stroke Unit, Department of Neurology, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, RICORS-ICTUS, Av. França s/n (7a Planta), 17007 Girona, Spain; (S.B.); (M.T.); (J.S.)
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Epigenetic Mechanisms of Epidermal Differentiation. Int J Mol Sci 2022; 23:ijms23094874. [PMID: 35563264 PMCID: PMC9102508 DOI: 10.3390/ijms23094874] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/24/2022] [Accepted: 04/27/2022] [Indexed: 12/12/2022] Open
Abstract
Keratinocyte differentiation is an essential process for epidermal stratification and stratum corneum formation. Keratinocytes proliferate in the basal layer of the epidermis and start their differentiation by changing their functional or phenotypical type; this process is regulated via induction or repression of epidermal differentiation complex (EDC) genes that play a pivotal role in epidermal development. Epidermal development and the keratinocyte differentiation program are orchestrated by several transcription factors, signaling pathways, and epigenetic regulators. The latter exhibits both activating and repressive effects on chromatin in keratinocytes via the ATP-dependent chromatin remodelers, histone demethylases, and genome organizers that promote terminal keratinocyte differentiation, and the DNA methyltransferases, histone deacetylases, and Polycomb components that stimulate proliferation of progenitor cells and inhibit premature activation of terminal differentiation-associated genes. In addition, microRNAs are involved in different processes between proliferation and differentiation during the program of epidermal development. Here, we bring together current knowledge of the mechanisms controlling gene expression during keratinocyte differentiation. An awareness of epigenetic mechanisms and their alterations in health and disease will help to bridge the gap between our current knowledge and potential applications for epigenetic regulators in clinical practice to pave the way for promising target therapies.
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Fatmi A, Chabni N, Cernada M, Vento M, González-López M, Aribi M, Pallardó FV, García-Giménez JL. Clinical and immunological aspects of microRNAs in neonatal sepsis. Biomed Pharmacother 2021; 145:112444. [PMID: 34808550 DOI: 10.1016/j.biopha.2021.112444] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/08/2021] [Accepted: 11/16/2021] [Indexed: 12/12/2022] Open
Abstract
Neonatal sepsis constitutes a highly relevant public health challenge and is the most common cause of infant morbidity and mortality worldwide. Recent studies have demonstrated that during infection epigenetic changes may occur leading to reprogramming of gene expression. Post-transcriptional regulation by short non-coding RNAs (e.g., microRNAs) have recently acquired special relevance because of their role in the regulation of the pathophysiology of sepsis and their potential clinical use as biomarkers. ~22-nucleotide of microRNAs are not only involved in regulating multiple relevant cellular and molecular functions, such as immune cell function and inflammatory response, but have also been proposed as good candidates as biomarkers in sepsis. Nevertheless, establishing clinical practice guidelines based on microRNA patterns as biomarkers for diagnosis and prognosis in neonatal sepsis has yet to be achieved. Given their differential expression across tissues in neonates, the release of specific microRNAs to blood and their expression pattern can differ compared to sepsis in adult patients. Further in-depth research is necessary to fully understand the biological relevance of microRNAs and assess their potential use in clinical settings. This review provides a general overview of microRNAs, their structure, function and biogenesis before exploring their potential clinical interest as diagnostic and prognostic biomarkers of neonatal sepsis. An important part of the review is focused on immune and inflammatory aspects of selected microRNAs that may become biomarkers for clinical use and therapeutic intervention.
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Affiliation(s)
- Ahlam Fatmi
- Laboratory of Applied Molecular Biology and Immunology, University of Tlemcen, W0414100, 13000 Tlemcen, Algeria
| | - Nafissa Chabni
- Faculty of Medicine, Tlemcen Medical Centre University, 13000 Tlemcen, Algeria
| | - María Cernada
- Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain; Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain, University and Polytechnic Hospital La Fe, Valencia, Spain
| | - Máximo Vento
- Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain; Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain, University and Polytechnic Hospital La Fe, Valencia, Spain
| | - María González-López
- Department of Pediatrics. Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Mourad Aribi
- Laboratory of Applied Molecular Biology and Immunology, University of Tlemcen, W0414100, 13000 Tlemcen, Algeria; Biotechnology Center of Constantine (CRBt), 25000 Constantine, Algeria
| | - Federico V Pallardó
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain; INCLIVA Health Research Institute, Mixed Unit for Rare Diseases INCLIVA-CIPF, Valencia, Spain; Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Valencia, Spain
| | - José Luis García-Giménez
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain; INCLIVA Health Research Institute, Mixed Unit for Rare Diseases INCLIVA-CIPF, Valencia, Spain; Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Valencia, Spain.
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Li J, Li L, Wang Y, Huang G, Li X, Xie Z, Zhou Z. Insights Into the Role of DNA Methylation in Immune Cell Development and Autoimmune Disease. Front Cell Dev Biol 2021; 9:757318. [PMID: 34790667 PMCID: PMC8591242 DOI: 10.3389/fcell.2021.757318] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/07/2021] [Indexed: 12/26/2022] Open
Abstract
To date, nearly 100 autoimmune diseases have been an area of focus, and these diseases bring health challenges to approximately 5% of the population worldwide. As a type of disease caused by tolerance breakdown, both environmental and genetic risk factors contribute to autoimmune disease development. However, in most cases, there are still gaps in our understanding of disease pathogenesis, diagnosis, and treatment. Therefore, more detailed knowledge of disease pathogenesis and potential therapies is indispensable. DNA methylation, which does not affect the DNA sequence, is one of the key epigenetic silencing mechanisms and has been indicated to play a key role in gene expression regulation and to participate in the development of certain autoimmune diseases. Potential epigenetic regulation via DNA methylation has garnered more attention as a disease biomarker in recent years. In this review, we clarify the basic function and distribution of DNA methylation, evaluate its effects on gene expression and discuss related key enzymes. In addition, we summarize recent aberrant DNA methylation modifications identified in the most important cell types related to several autoimmune diseases and then provide potential directions for better diagnosing and monitoring disease progression driven by epigenetic control, which may broaden our understanding and contribute to further epigenetic research in autoimmune diseases.
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Affiliation(s)
- Jiaqi Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Lifang Li
- Department of Ultrasound, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yimeng Wang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Gan Huang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhiguo Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
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Corley MJ, Pang APS, Rasmussen TA, Tolstrup M, Søgaard OS, Ndhlovu LC. Candidate host epigenetic marks predictive for HIV reservoir size, responsiveness to latency reversal, and viral rebound. AIDS 2021; 35:2269-2279. [PMID: 34482353 PMCID: PMC8563431 DOI: 10.1097/qad.0000000000003065] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE This study aimed to identify candidate host epigenetic biomarkers predicting latency reversal agents (LRA) efficacy and HIV-1 rebound kinetics during analytical treatment interruption (ATI). DESIGN Retrospective longitudinal epigenetic profiling study from 13 people with HIV (PWH) on virologically suppressive antiretroviral therapy (ART) that participated in a LRA (HDAC inhibitor) clinical trial (NCT01680094) and a subsequent optional ATI to monitor for viral recrudescence after ART cessation. METHODS Genome-wide DNA methylation (DNAm) in purified CD4+ T cells was measured at single-nucleotide resolution using the Infinium MethylationEPIC array. HIV-1 DNA and RNA measures were previously assessed by PCR-based methods and the association of DNAm levels at regulatory sites of the human genome were examined with reservoir size, responsiveness to LRA, and time to viral rebound following ATI. RESULTS A distinct set of 15 candidate DNAm sites in purified CD4+ T cells at baseline pre-LRA and pre-ATI significantly correlated with time to viral rebound. Eight of these DNAm sites occurred in genes linked to HIV-1 replication dynamics including (SEPSECS, cg19113954), (MALT1, cg15968021), (CPT1C, cg14318858), (CRTAM, cg10977115), (B4GALNT4, cg04663285), (IL10, cg16284789), (TFPI2, cg19645693), and (LIFR, cg26437306); with the remaining sites at intergenic regions containing regulatory elements. Moreover, baseline DNAm states related to total HIV-1 DNA levels and the fold change in unspliced cell-associated HIV RNA following LRA treatment. CONCLUSION Preexisting host epigenetic states may determine HIV-1 rebound kinetics and reservoir maintenance. These findings suggest integrating a suite of DNA methylation markers to improve optimal participant selection and drug regimen in future HIV cure clinical trials.
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Affiliation(s)
- Michael J. Corley
- Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, New York, USA
| | - Alina PS Pang
- Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, New York, USA
| | - Thomas A. Rasmussen
- The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC 3000, Australia
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | - Martin Tolstrup
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | - Ole S. Søgaard
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Lishomwa C. Ndhlovu
- Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, New York, USA
- Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii
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DNA Methylation and Type 2 Diabetes: Novel Biomarkers for Risk Assessment? Int J Mol Sci 2021; 22:ijms222111652. [PMID: 34769081 PMCID: PMC8584054 DOI: 10.3390/ijms222111652] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/25/2021] [Accepted: 10/25/2021] [Indexed: 12/15/2022] Open
Abstract
Diabetes is a severe threat to global health. Almost 500 million people live with diabetes worldwide. Most of them have type 2 diabetes (T2D). T2D patients are at risk of developing severe and life-threatening complications, leading to an increased need for medical care and reduced quality of life. Improved care for people with T2D is essential. Actions aiming at identifying undiagnosed diabetes and at preventing diabetes in those at high risk are needed as well. To this end, biomarker discovery and validation of risk assessment for T2D are critical. Alterations of DNA methylation have recently helped to better understand T2D pathophysiology by explaining differences among endophenotypes of diabetic patients in tissues. Recent evidence further suggests that variations of DNA methylation might contribute to the risk of T2D even more significantly than genetic variability and might represent a valuable tool to predict T2D risk. In this review, we focus on recent information on the contribution of DNA methylation to the risk and the pathogenesis of T2D. We discuss the limitations of these studies and provide evidence supporting the potential for clinical application of DNA methylation marks to predict the risk and progression of T2D.
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Rodríguez ML, Millán I, Ortega ÁL. Cellular targets in diabetic retinopathy therapy. World J Diabetes 2021; 12:1442-1462. [PMID: 34630899 PMCID: PMC8472497 DOI: 10.4239/wjd.v12.i9.1442] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/08/2021] [Accepted: 08/03/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the existence of treatment for diabetes, inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy. Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles. Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease. Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia. The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy. Therefore, in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that, potentially, can prevent the development and progression of the disease.
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Affiliation(s)
- María Lucía Rodríguez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
| | - Iván Millán
- Neonatal Research Group, Health Research Institute La Fe, Valencia 46026, Valencia, Spain
| | - Ángel Luis Ortega
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
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10
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Reuter C, Preece M, Banwait R, Boer S, Cuzick J, Lorincz A, Nedjai B. Consistency of the S5 DNA methylation classifier in formalin-fixed biopsies versus corresponding exfoliated cells for the detection of pre-cancerous cervical lesions. Cancer Med 2021; 10:2668-2679. [PMID: 33710792 PMCID: PMC8026949 DOI: 10.1002/cam4.3849] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 02/10/2021] [Accepted: 02/23/2021] [Indexed: 12/11/2022] Open
Abstract
Methylation biomarkers are promising tools for diagnosis and disease prevention. The S5 classifier is aimed at the prevention of cervical cancer by the early detection of cervical intraepithelial neoplasia (CIN). S5 is based on pyrosequencing a promoter region of EPB41L3 and five late regions of HPV types 16, 18, 31, and 33 following bisulfite conversion of DNA. Good biomarkers should perform well in a variety of sample types such as exfoliated cells, fresh frozen or formalin-fixed paraffin-embedded (FFPE) materials. Here, we tested the performance of S5 on 315 FFPE biopsies with paired exfoliated cervical samples using four different conversion kits (Epitect Bisulfite, Epitect Fast Bisulfite, EZ DNA Methylation, and EZ DNA Methylation-Lightning). The S5 values from FFPE biopsies for all kits were significantly correlated with those obtained from their paired exfoliated cells. For the EZ DNA Methylation kit, we observed an average increased methylation of 4.4% in FFPE. This was due to incomplete conversion of DNA (73% for FFPE vs. 95% for cells). The other kits had a DNA conversion rate in FFPE similar to the cells (95%-97%). S5 performed well at discriminating
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Affiliation(s)
- Caroline Reuter
- Centre for Cancer PreventionWolfson Institute of Preventive MedicineQueen Mary University of LondonLondonUK
| | - Matthew Preece
- Centre for Cancer PreventionWolfson Institute of Preventive MedicineQueen Mary University of LondonLondonUK
| | - Rawinder Banwait
- Centre for Cancer PreventionWolfson Institute of Preventive MedicineQueen Mary University of LondonLondonUK
| | - Sabrina Boer
- Department of UrologyRadboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenthe Netherlands
| | - Jack Cuzick
- Centre for Cancer PreventionWolfson Institute of Preventive MedicineQueen Mary University of LondonLondonUK
| | - Attila Lorincz
- Centre for Cancer PreventionWolfson Institute of Preventive MedicineQueen Mary University of LondonLondonUK
| | - Belinda Nedjai
- Centre for Cancer PreventionWolfson Institute of Preventive MedicineQueen Mary University of LondonLondonUK
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11
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Traversi D, Pulliero A, Izzotti A, Franchitti E, Iacoviello L, Gianfagna F, Gialluisi A, Izzi B, Agodi A, Barchitta M, Calabrò GE, Hoxhaj I, Sassano M, Sbrogiò LG, Del Sole A, Marchiori F, Pitini E, Migliara G, Marzuillo C, De Vito C, Tamburro M, Sammarco ML, Ripabelli G, Villari P, Boccia S. Precision Medicine and Public Health: New Challenges for Effective and Sustainable Health. J Pers Med 2021; 11:135. [PMID: 33669364 PMCID: PMC7920275 DOI: 10.3390/jpm11020135] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 02/11/2021] [Accepted: 02/14/2021] [Indexed: 02/06/2023] Open
Abstract
The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high levels of skill and economic investment initially necessary. The fields of human genetics and public health have highlighted the relevance of an implementation strategy at a national level in Italy, including integration in sanitary regulations and governance instruments. In this review, the emerging field of public health genomics is discussed, including the polygenic scores approach, epigenetic modulation, nutrigenomics, and microbiomes implications. Moreover, the Italian state of implementation is presented. The omics sciences have important implications for the prevention of both communicable and noncommunicable diseases, especially because they can be used to assess the health status during the whole course of life. An effective population health gain is possible if omics tools are implemented for each person after a preliminary assessment of effectiveness in the medium to long term.
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Affiliation(s)
- Deborah Traversi
- Department of Public Health and Pediatrics, University of Torino, Piazza Polonia 94, 10126 Torino, Italy;
| | - Alessandra Pulliero
- Department of Health Sciences School of Medicine, University of Genoa, 16132 Genova, Italy;
| | - Alberto Izzotti
- Department of Experimental Medicine, University of Genoa, 16132 Genova, Italy;
- IRCCS Ospedale Policlinico San Martino, 161632 Genova, Italy
| | - Elena Franchitti
- Department of Public Health and Pediatrics, University of Torino, Piazza Polonia 94, 10126 Torino, Italy;
| | - Licia Iacoviello
- Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy; (L.I.); (F.G.)
- Department of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, Italy; (A.G.); (B.I.)
| | - Francesco Gianfagna
- Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy; (L.I.); (F.G.)
- Mediterranea Cardiocentro, 80122 Napoli, Italy
| | - Alessandro Gialluisi
- Department of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, Italy; (A.G.); (B.I.)
| | - Benedetta Izzi
- Department of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, Italy; (A.G.); (B.I.)
| | - Antonella Agodi
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, 95123 Catania, Italy; (A.A.); (M.B.)
| | - Martina Barchitta
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, 95123 Catania, Italy; (A.A.); (M.B.)
| | - Giovanna Elisa Calabrò
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (G.E.C.); (I.H.); (M.S.); (S.B.)
| | - Ilda Hoxhaj
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (G.E.C.); (I.H.); (M.S.); (S.B.)
| | - Michele Sassano
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (G.E.C.); (I.H.); (M.S.); (S.B.)
| | - Luca Gino Sbrogiò
- Dipartimento di Prevenzione, Az. ULSS3 Serenissima, 30174 Venezia, Italy;
| | | | | | - Erica Pitini
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy; (E.P.); (G.M.); (C.M.); (C.D.V.); (P.V.)
| | - Giuseppe Migliara
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy; (E.P.); (G.M.); (C.M.); (C.D.V.); (P.V.)
| | - Carolina Marzuillo
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy; (E.P.); (G.M.); (C.M.); (C.D.V.); (P.V.)
| | - Corrado De Vito
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy; (E.P.); (G.M.); (C.M.); (C.D.V.); (P.V.)
| | - Manuela Tamburro
- Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, 86100 Campobasso, Italy; (M.T.); (M.L.S.); (G.R.)
| | - Michela Lucia Sammarco
- Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, 86100 Campobasso, Italy; (M.T.); (M.L.S.); (G.R.)
| | - Giancarlo Ripabelli
- Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, 86100 Campobasso, Italy; (M.T.); (M.L.S.); (G.R.)
| | - Paolo Villari
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Roma, Italy; (E.P.); (G.M.); (C.M.); (C.D.V.); (P.V.)
| | - Stefania Boccia
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (G.E.C.); (I.H.); (M.S.); (S.B.)
- Department of Woman and Child Health and Public Health-Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy
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12
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Rahat B, Ali T, Sapehia D, Mahajan A, Kaur J. Circulating Cell-Free Nucleic Acids as Epigenetic Biomarkers in Precision Medicine. Front Genet 2020; 11:844. [PMID: 32849827 PMCID: PMC7431953 DOI: 10.3389/fgene.2020.00844] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 07/13/2020] [Indexed: 12/20/2022] Open
Abstract
The circulating cell-free nucleic acids (ccfNAs) are a mixture of single- or double-stranded nucleic acids, released into the blood plasma/serum by different tissues via apoptosis, necrosis, and secretions. Under healthy conditions, ccfNAs originate from the hematopoietic system, whereas under various clinical scenarios, the concomitant tissues release ccfNAs into the bloodstream. These ccfNAs include DNA, RNA, microRNA (miRNA), long non-coding RNA (lncRNA), fetal DNA/RNA, and mitochondrial DNA/RNA, and act as potential biomarkers in various clinical conditions. These are associated with different epigenetic modifications, which show disease-related variations and so finding their role as epigenetic biomarkers in clinical settings. This field has recently emerged as the latest advance in precision medicine because of its clinical relevance in diagnostic, prognostic, and predictive values. DNA methylation detected in ccfDNA has been widely used in personalized clinical diagnosis; furthermore, there is also the emerging role of ccfRNAs like miRNA and lncRNA as epigenetic biomarkers. This review focuses on the novel approaches for exploring ccfNAs as epigenetic biomarkers in personalized clinical diagnosis and prognosis, their potential as therapeutic targets and disease progression monitors, and reveals the tremendous potential that epigenetic biomarkers present to improve precision medicine. We explore the latest techniques for both quantitative and qualitative detection of epigenetic modifications in ccfNAs. The data on epigenetic modifications on ccfNAs are complex and often milieu-specific posing challenges for its understanding. Artificial intelligence and deep networks are the novel approaches for decoding complex data and providing insight into the decision-making in precision medicine.
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Affiliation(s)
- Beenish Rahat
- National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Taqveema Ali
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Divika Sapehia
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aatish Mahajan
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jyotdeep Kaur
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
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13
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Beltrán-García J, Osca-Verdegal R, Nacher-Sendra E, Pallardó FV, García-Giménez JL. Circular RNAs in Sepsis: Biogenesis, Function, and Clinical Significance. Cells 2020; 9:cells9061544. [PMID: 32630422 PMCID: PMC7349763 DOI: 10.3390/cells9061544] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 06/23/2020] [Accepted: 06/24/2020] [Indexed: 01/08/2023] Open
Abstract
Sepsis is a life-threatening condition that occurs when the body responds to an infection that damages it is own tissues. The major problem in sepsis is rapid, vital status deterioration in patients, which can progress to septic shock with multiple organ failure if not properly treated. As there are no specific treatments, early diagnosis is mandatory to reduce high mortality. Despite more than 170 different biomarkers being postulated, early sepsis diagnosis and prognosis remain a challenge for clinicians. Recent findings propose that circular RNAs (circRNAs) may play a prominent role in regulating the patients’ immune system against different pathogens, including bacteria and viruses. Mounting evidence also suggests that the misregulation of circRNAs is an early event in a wide range of diseases, including sepsis. Despite circRNA levels being altered in sepsis, the specific mechanisms controlling the dysregulation of these noncoding RNAs are not completely elucidated, although many factors are known to affect circRNA biogenesis. Therefore, there is a need to explore the molecular pathways that lead to this disorder. This review describes the role of this new class of regulatory RNAs in sepsis and the feasibility of using circRNAs as diagnostic biomarkers for sepsis, opening up new avenues for circRNA-based medicine.
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Affiliation(s)
- Jesús Beltrán-García
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain; (J.B.-G.); (F.V.P.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain;
- Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, 46010 València, Spain;
| | - Rebeca Osca-Verdegal
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain;
- Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, 46010 València, Spain;
| | - Elena Nacher-Sendra
- Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, 46010 València, Spain;
| | - Federico V. Pallardó
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain; (J.B.-G.); (F.V.P.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain;
- Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, 46010 València, Spain;
| | - José Luis García-Giménez
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain; (J.B.-G.); (F.V.P.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain;
- Departamento de Fisiología, Facultad de Medicina y Odontología, Universitat de València, 46010 València, Spain;
- Correspondence:
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14
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Beltrán-García J, Osca-Verdegal R, Romá-Mateo C, Carbonell N, Ferreres J, Rodríguez M, Mulet S, García-López E, Pallardó FV, García-Giménez JL. Epigenetic biomarkers for human sepsis and septic shock: insights from immunosuppression. Epigenomics 2020; 12:617-646. [PMID: 32396480 DOI: 10.2217/epi-2019-0329] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Sepsis is a life-threatening condition that occurs when the body responds to an infection damaging its own tissues. Sepsis survivors sometimes suffer from immunosuppression increasing the risk of death. To our best knowledge, there is no 'gold standard' for defining immunosuppression except for a composite clinical end point. As the immune system is exposed to epigenetic changes during and after sepsis, research that focuses on identifying new biomarkers to detect septic patients with immunoparalysis could offer new epigenetic-based strategies to predict short- and long-term pathological events related to this life-threatening state. This review describes the most relevant epigenetic mechanisms underlying alterations in the innate and adaptive immune responses described in sepsis and septic shock, and their consequences for immunosuppression states, providing several candidates to become epigenetic biomarkers that could improve sepsis management and help predict immunosuppression in postseptic patients.
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Affiliation(s)
- Jesús Beltrán-García
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia 46010, Spain.,Department of Physiology, Faculty of Medicine & Dentistry, University of Valencia, Valencia 46010, Spain.,INCLIVA Biomedical Research Institute, Valencia 46010, Spain.,EpiDisease S.L. (Spin-Off CIBER-ISCIII), Parc Científic de la Universitat de València, Paterna 46980, Valencia, Spain
| | - Rebeca Osca-Verdegal
- Department of Physiology, Faculty of Medicine & Dentistry, University of Valencia, Valencia 46010, Spain
| | - Carlos Romá-Mateo
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia 46010, Spain.,Department of Physiology, Faculty of Medicine & Dentistry, University of Valencia, Valencia 46010, Spain.,INCLIVA Biomedical Research Institute, Valencia 46010, Spain
| | - Nieves Carbonell
- INCLIVA Biomedical Research Institute, Valencia 46010, Spain.,Intensive Care Unit, Clinical University Hospital of Valencia, Valencia 46010, Spain
| | - José Ferreres
- INCLIVA Biomedical Research Institute, Valencia 46010, Spain.,Intensive Care Unit, Clinical University Hospital of Valencia, Valencia 46010, Spain
| | - María Rodríguez
- INCLIVA Biomedical Research Institute, Valencia 46010, Spain.,Intensive Care Unit, Clinical University Hospital of Valencia, Valencia 46010, Spain
| | - Sandra Mulet
- INCLIVA Biomedical Research Institute, Valencia 46010, Spain.,Intensive Care Unit, Clinical University Hospital of Valencia, Valencia 46010, Spain
| | - Eva García-López
- EpiDisease S.L. (Spin-Off CIBER-ISCIII), Parc Científic de la Universitat de València, Paterna 46980, Valencia, Spain
| | - Federico V Pallardó
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia 46010, Spain.,Department of Physiology, Faculty of Medicine & Dentistry, University of Valencia, Valencia 46010, Spain.,INCLIVA Biomedical Research Institute, Valencia 46010, Spain
| | - José Luis García-Giménez
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia 46010, Spain.,Department of Physiology, Faculty of Medicine & Dentistry, University of Valencia, Valencia 46010, Spain.,INCLIVA Biomedical Research Institute, Valencia 46010, Spain.,EpiDisease S.L. (Spin-Off CIBER-ISCIII), Parc Científic de la Universitat de València, Paterna 46980, Valencia, Spain
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15
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16
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Kilzheimer A, Hentrich T, Burkhardt S, Schulze-Hentrich JM. The Challenge and Opportunity to Diagnose Parkinson's Disease in Midlife. Front Neurol 2019; 10:1328. [PMID: 31920948 PMCID: PMC6928126 DOI: 10.3389/fneur.2019.01328] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 12/02/2019] [Indexed: 12/16/2022] Open
Abstract
Parkinson's disease (PD) is the most common neurodegenerative movement disorder that affects extensive regions of the nervous system. Its current clinical diagnosis is based on motor symptoms that appear late during disease progression when substantial proportions of the nigrostriatal dopaminergic neuron population are lost already. Although disturbances in sleep and other biofunctions often surface years prior to motor impairments and point to a long prodromal phase, these phenotypic signs in a person's midlife lack predictive power. They do, however, signal the unfolding of the disease and suggest molecular correlates that begin deviating early on. Revealing such trajectories, hence, promises not only a better understanding of prodromal PD but may also enable a much-needed earlier diagnosis. A nexus that may harbor such molecular trajectories is the epigenome as key etiological factors of PD-genetics, age, and environment-influence this substrate. An earlier diagnosis would also allow earlier interventions and lifestyle adjustments to improve brain function and reduce symptoms. In this review, we describe the challenges of diagnosing PD early on and highlight the opportunities that may arise from steering research efforts towards comprehensive interrogations of molecular layers during the long-time neglected midlife phase. In particular, we emphasize how existing cohorts of at-risk individuals, available animal models, and suitable markers may come together and aid in revealing molecular trajectories that offer diagnostic utility for PD in its prodromal stage.
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17
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Soler-Botija C, Gálvez-Montón C, Bayés-Genís A. Epigenetic Biomarkers in Cardiovascular Diseases. Front Genet 2019; 10:950. [PMID: 31649728 PMCID: PMC6795132 DOI: 10.3389/fgene.2019.00950] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 09/05/2019] [Indexed: 12/16/2022] Open
Abstract
Cardiovascular diseases are the number one cause of death worldwide and greatly impact quality of life and medical costs. Enormous effort has been made in research to obtain new tools for efficient and quick diagnosis and predicting the prognosis of these diseases. Discoveries of epigenetic mechanisms have related several pathologies, including cardiovascular diseases, to epigenetic dysregulation. This has implications on disease progression and is the basis for new preventive strategies. Advances in methodology and big data analysis have identified novel mechanisms and targets involved in numerous diseases, allowing more individualized epigenetic maps for personalized diagnosis and treatment. This paves the way for what is called pharmacoepigenetics, which predicts the drug response and develops a tailored therapy based on differences in the epigenetic basis of each patient. Similarly, epigenetic biomarkers have emerged as a promising instrument for the consistent diagnosis and prognosis of cardiovascular diseases. Their good accessibility and feasible methods of detection make them suitable for use in clinical practice. However, multicenter studies with a large sample population are required to determine with certainty which epigenetic biomarkers are reliable for clinical routine. Therefore, this review focuses on current discoveries regarding epigenetic biomarkers and its controversy aiming to improve the diagnosis, prognosis, and therapy in cardiovascular patients.
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Affiliation(s)
- Carolina Soler-Botija
- Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
| | - Carolina Gálvez-Montón
- Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
| | - Antoni Bayés-Genís
- Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
- CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
- Cardiology Service, HUGTiP, Badalona, Spain
- Department of Medicine, Barcelona Autonomous University (UAB), Badalona, Spain
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18
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Beltrán-García J, Osca-Verdegal R, Mena-Mollá S, García-Giménez JL. Epigenetic IVD Tests for Personalized Precision Medicine in Cancer. Front Genet 2019; 10:621. [PMID: 31316555 PMCID: PMC6611494 DOI: 10.3389/fgene.2019.00621] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 06/13/2019] [Indexed: 12/12/2022] Open
Abstract
Epigenetic alterations play a key role in the initiation and progression of cancer. Therefore, it is possible to use epigenetic marks as biomarkers for predictive and precision medicine in cancer. Precision medicine is poised to impact clinical practice, patients, and healthcare systems. The objective of this review is to provide an overview of the epigenetic testing landscape in cancer by examining commercially available epigenetic-based in vitro diagnostic tests for colon, breast, cervical, glioblastoma, lung cancers, and for cancers of unknown origin. We compile current commercial epigenetic tests based on epigenetic biomarkers (i.e., DNA methylation, miRNAs, and histones) that can actually be implemented into clinical practice.
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Affiliation(s)
- Jesús Beltrán-García
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain.,INCLIVA Biomedical Research Institute, Valencia, Spain.,Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain
| | - Rebeca Osca-Verdegal
- INCLIVA Biomedical Research Institute, Valencia, Spain.,Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain
| | - Salvador Mena-Mollá
- Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain.,EpiDisease S.L. Spin-Off of CIBERER (ISCIII), Valencia, Spain
| | - José Luis García-Giménez
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain.,INCLIVA Biomedical Research Institute, Valencia, Spain.,Department of Physiology, School of Medicine and Dentistry, Universitat de València (UV), Valencia, Spain.,EpiDisease S.L. Spin-Off of CIBERER (ISCIII), Valencia, Spain
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19
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20
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Paiva S, Agbulut O. MiRroring the Multiple Potentials of MicroRNAs in Acute Myocardial Infarction. Front Cardiovasc Med 2017; 4:73. [PMID: 29209617 PMCID: PMC5701911 DOI: 10.3389/fcvm.2017.00073] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Accepted: 10/31/2017] [Indexed: 12/28/2022] Open
Abstract
At present, cardiovascular diseases are depicted to be the leading cause of death worldwide according to the World Health Organization. In the future, projections predict that ischemic heart disease will persist in the top main causes of illness. Within this alarming context, some tiny master regulators of gene expression programs, namely, microRNAs (miRNAs) carry three promising potentials. In fact, miRNAs can prove to be useful not only in terms of biomarkers allowing heart injury detection but also in terms of therapeutics to overcome limitations of past strategies and treat the lesions. In a more creative approach, they can even be used in the area of human engineered cardiac tissues as maturation tools for cardiomyocytes (CMs) derived from pluripotent stem cell. Very promising not only for patient-specific cell-based therapies but also to develop biomimetic microsystems for disease modeling and drug screening, these cells greatly contribute to personalized medicine. To get into the heart of the matter, the focus of this review lies primarily on miRNAs as acute myocardial infarction (AMI) biomarkers. Only large cohort studies comprising over 100 individuals to reach a potent statistical value were considered. Certain miRNAs appeared to possibly complement protein-based biomarkers and classical risk factors. Some were even described to bear potential in the discrimination of similar symptomatic pathologies. However, differences between pre-analytical and analytical approaches substantially influenced miRNA data. Further supported by meta-analysis studies, this problem had to be addressed. A detailed critical analysis of each step to define miRNAs biomarker potential is provided to inspire a future improved universal strategy. Interestingly, a recurrent set of cardiomyocyte-enriched miRNAs was found, namely, miR-1; miR-133; miR-208a/b; and miR-499a. Each member of this myomiRs group displayed promising roles either individually or in combination as AMI diagnostic or prognostic biomarkers. Furthermore, a precise combo was shown to be powerful enough to transdifferentiate human fibroblasts into CMs opening doors in the therapeutics. Following these discoveries, they also emerged as optional tools to transfect in order to mature CMs derived from pluripotent stem cells. Ultimately, the multiple potentials carried by the myomiRs miR-1; miR-133; miR-208a/b; and miR-499a still remain to be fully unveiled.
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Affiliation(s)
- Solenne Paiva
- Sorbonne Universités, UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR CNRS 8256, Biological Adaptation and Aging, Paris, France
| | - Onnik Agbulut
- Sorbonne Universités, UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR CNRS 8256, Biological Adaptation and Aging, Paris, France
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