Article
Cardiac & Cardiovascular Systems
Adam Russell-Hallinan, Roisin Neary, Chris J. Watson, John A. Baugh
Summary: The study demonstrates the association of pressure overload-induced pathological cardiac remodeling with increased DNA methylation and the potential of low-dose 5aza treatment in attenuating myocardial hypertrophy and fibrosis, along with reduction in global DNA methylation levels and DNA methyltransferase expression in the heart.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Le Li, Qipeng Wu, Chunmeng Miao, Muhammad Hasnat, Luyong Zhang, Zhenzhou Jiang, Qinwei Yu
Summary: The level of DNA methylation can influence the expression of tumor promoting and tumor suppressor genes. DNA methyltransferase inhibitors can reduce high methylation levels in cancer cells and inhibit the progression of various cancers, including hepatocellular carcinoma (HCC). However, the pro-metastatic effect of DNA methyltransferase inhibitors in some cancers suggests potential risks. Our study aims to investigate the effect of the DNA methyltransferase inhibitor 5-Aza-cytidine on HCC metastasis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Chih-Chin Hsu, Jong-Shyan Wang, Yu-Chiau Shyu, Tieh-Cheng Fu, Yu-Hsiang Juan, Shin-Sheng Yuan, Chao-Hung Wang, Chi-Hsiao Yeh, Po-Cheng Liao, Hsin-Yi Wu, Pang-Hung Hsu
Summary: This translational research examined the implications of DNA methylation associated with high-intensity interval training (HIIT) on cardiac fibrosis in patients with heart failure (HF). The study found that HIIT can reduce cardiac fibrosis and improve cardiorespiratory fitness. This was confirmed through a variety of tests on HF patients, including cardiovascular magnetic resonance imaging and cardiopulmonary exercise tests, as well as cell experiments and proteomics analysis.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Cell Biology
Adam P. Sharples, Daniel C. Turner
Summary: Skeletal muscle memory is a phenomenon that has caught the attention of the scientific community, exercise practitioners, and the public. Research has shown that previous positive experiences with exercise training can enhance the adaptability of skeletal muscle tissue to later retraining, even after a period of exercise cessation or detraining. This review discusses the cellular and epigenetic mechanisms of skeletal muscle memory, as well as the importance of investigating muscle memory for optimizing exercise interventions and developing strategies for muscle wasting conditions and age-related muscle loss. The review also highlights future directions for research in skeletal muscle memory.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Oncology
Maximilian Schmutz, Manuela Zucknick, Richard F. Schlenk, Daniel Mertens, Axel Benner, Dieter Weichenhan, Oliver Muecke, Konstanze Doehner, Christoph Plass, Lars Bullinger, Rainer Claus
Summary: In this study, the researchers investigated whether unbiased genome-wide assessment of pre-treatment DNA methylation profiles can help identify AML patients who will achieve remission after an azacytidine-containing induction regimen. They found that some AML patients benefit from this treatment, but no predictive biomarkers for therapy response exist. The researchers also evaluated the value of a whole genome methyl-CpG screening assay and compared the discriminatory power of differentially methylated regions (DMRs) and single CpGs for predicting therapy response. The results suggest that a predictive epigenotype carries its methylation information at a complex, genome-wide level. However, the specificity of the predictive response to therapy was lacking for treatment with azacytidine.
CLINICAL EPIGENETICS
(2023)
Article
Peripheral Vascular Disease
Michelle L. Roberts, Theodore A. Kotchen, Xiaoqing Pan, Yingchuan Li, Chun Yang, Pengyuan Liu, Tao Wang, Purushottam W. Laud, Thomas H. Chelius, Yannick Munyura, David L. Mattson, Yong Liu, Allen W. Cowley, Srividya Kidambi, Mingyu Liang
Summary: This study identified DNA methylation regions that are significantly associated with 24-hour blood pressure phenotypes, which may serve as important markers for blood pressure regulation. The newly developed methylation sequencing method has potential for clinical testing and large-scale population screenings.
Article
Biotechnology & Applied Microbiology
Kazutoshi Yamagishi, Yoshio Kikuta
Summary: Epigenetic modifications, such as DNA methylation, play a role in regulating gene expression in animals and plants. This study demonstrated that treatment with 5-aza-Cd can reactivate a silenced transgene in tobacco cells, but the reactivation is transient and can be attenuated over time. Additionally, derivatives of 5-mCs, such as 5-mCd and 5-mdCd, were shown to inhibit or reverse the reactivation induced by 5-aza-Cd.
PLANT BIOTECHNOLOGY
(2021)
Article
Medicine, General & Internal
Dae-Yeon Kim, Hee-Tae Cheong, Chang-Six Ra, Kazuhiro Kimura, Bae Dong Jung
Summary: The study revealed that inhibition of UCP2 expression in Hep3B cells was due to methylation of the promoter region, and treatment with 5-aza could increase UCP2 expression, which may have implications for cancer treatment.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Genetics & Heredity
Alana C. Jones, Amit Patki, Steven A. Claas, Hemant K. Tiwari, Ninad S. Chaudhary, Devin M. Absher, Leslie A. Lange, Ethan M. Lange, Wei Zhao, Scott M. Ratliff, Sharon L. R. Kardia, Jennifer A. Smith, Marguerite R. Irvin, Donna K. Arnett
Summary: Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular disease, and African Americans have a higher risk of LVH. This study used methylation and echocardiography data to identify differentially methylated regions (DMRs) associated with LVH in African Americans. The results suggest potential candidate genes and variants related to LVH and highlight the importance of DNA methylation patterns in the development of LVH.
Article
Biochemistry & Molecular Biology
Jaafar Al-Hasani, Carla Sens-Albert, Subhajit Ghosh, Felix A. Trogisch, Taslima Nahar, Prisca A. P. Friede, Jan-Christian Reil, Markus Hecker
Summary: Zyxin knockout mice exhibit cardiac dysfunction due to enhanced cardiomyocyte apoptosis and excessive fibrosis during hypertension.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Genetics & Heredity
Shi-Yi Lyu, Wang Xiao, Guang-Zu Cui, Cheng Yu, Huan Liu, Min Lyu, Qian-Ya Kuang, En-Hua Xiao, Yong-Heng Luo
Summary: Liver fibrosis is a repair response to various chronic liver injuries, and the activation and transformation of hepatic stellate cells (HSCs) play a key role in this process. Epigenetic regulation, especially DNA methylation, has been found to be involved in HSC activation and liver fibrosis by affecting the expression of related genes. This review discusses the mechanism of DNA methylation in liver fibrosis pathogenesis, explores DNA methylation inhibitors as potential therapies, and provides insights for the prevention and clinical treatment of liver fibrosis.
FRONTIERS IN GENETICS
(2023)
Article
Pharmacology & Pharmacy
Ai Wei, Qi Gao, Fang Chen, Xiaobo Zhu, Xingren Chen, Lijun Zhang, Xin Su, Jinghong Dai, Yi Shi, Wangsen Cao
Summary: This study investigates the role of DNA methylation aberration-associated suppression of PPAR gamma in pulmonary fibrosis. The researchers found that aberrant DNA methylation and subsequent suppression of PPAR gamma significantly contribute to the development of pulmonary fibrosis. Restoring PPAR gamma expression through the use of demethylating agents or natural compounds can alleviate the pathological changes associated with fibrosis.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Wubin Ding, Diljeet Kaur, Steve Horvath, Wanding Zhou
Summary: Researchers have developed informatics infrastructure and methods for DNA methylation analysis in multiple species, including domesticated animals and laboratory mice. They have created a data-driven analysis pipeline for species inference, genome-specific data preprocessing, and regression modeling. Comparative analysis has revealed the dynamics of epigenome evolution in different genomic territories and tissue types, and specific methylation differences related to mouse strain phenotypes have been identified. These methods expand epigenome research to a wide range of species by streamlining DNA methylation array analysis for undesigned genomes.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Cell Biology
Hui Tao, Peng Shi, Xu-Dong Zhao, Hai-Yang Xuan, Wen-Hui Gong, Xuan-Sheng Ding
Summary: Cardiac fibrosis is a key pathological manifestation of diabetic cardiomyopathy, and research indicates that DNMT1-mediated suppression of SOCS3 promoter hypermethylation is a driver of cardiac fibroblast activation in diabetic cardiac fibrosis. This study provides new insights into the underlying mechanism of diabetic cardiac fibrosis.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Immunology
Shivanthan Shanthikumar, Melanie R. Neeland, Richard Saffery, Sarath C. Ranganathan, Alicia Oshlack, Jovana Maksimovic
Summary: In this study, bronchoalveolar lavage samples were used to define DNA methylation profiles for common cell types in the lungs, facilitating reference-based cell type composition estimation. These profiles were then successfully utilized in conjunction with an established methylation deconvolution method to estimate cell type composition in different tissue types, enabling further study of DNA methylation's role in lung health and disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Joseph McCambridge, Ciara Keane, Myra Walshe, Patricia Campbell, James Heyes, Paul R. Kalra, Martin R. Cowie, Jillian P. Riley, Rory O'Hanlon, Mark Ledwidge, Joseph Gallagher, Kenneth McDonald
Summary: The study aimed to analyze community management of patients with acute decompensated heart failure (ADHF) prior to admission. It found that a majority of patients did not recognize dyspnoea as a symptom of heart failure, and there were challenges in GP management of HF patients, with barriers including inadequate access to diagnostics and specialist support. The findings suggest a potential for earlier intervention and prevention of hospitalization in ADHF.
Article
Cardiac & Cardiovascular Systems
Chris Watson, J. Paul Spiers, Max Waterstone, Adam Russell-Hallinan, Joseph Gallagher, Kenneth McDonald, Cristin Ryan, John Gilmer, Mark Ledwidge
Summary: The study found that the minor allele of the rs3918242 genetic variant in the promoter region of the MMP-9 gene is associated with an increased risk of myocardial infarction, decreased ejection fraction, and progression of left ventricular systolic dysfunction in diabetes patients. This suggests that MMP-9 may serve as a biomarker for ventricular dysfunction and a potential target for heart failure prevention in diabetes.
BMC CARDIOVASCULAR DISORDERS
(2021)
Article
Medicine, Research & Experimental
Chris J. Watson, Joe Gallagher, Mark Wilkinson, Adam Russell-Hallinan, Isaac Tea, Stephanie James, James O'Reilly, Eoin O'Connell, Shuaiwei Zhou, Mark Ledwidge, Ken McDonald
Summary: The study found that BNP, hsTroponin-I, and Galectin-3 are important predictors in forecasting future HFpEF in asymptomatic individuals with cardiovascular disease risk factors. On the other hand, Interleukin-6 and sST2 did not show predictive value in this study.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Claire Tonry, Ken McDonald, Mark Ledwidge, Belinda Hernandez, Nadezhda Glezeva, Cathy Rooney, Brian Morrissey, Stephen R. Pennington, John A. Baugh, Chris J. Watson
Summary: This study aimed to design a mass spectrometry-based method to measure protein biomarkers of heart failure and found significant differences in some proteins between heart failure and non-heart failure patients. The combination of BNP measurement with a set of biomarkers was more accurate in predicting heart failure compared to BNP alone.
Article
Medicine, General & Internal
Joe Gallagher, Master Chisale, Sudipto Das, Richard J. Drew, Nadezhda Gleseva, Dermot Michael Wildes, Cillian De Gascun, Tsung-Shu Joseph Wu, Mark T. Ledwidge, Chris Watson
Summary: The study in primary care in Northern Malawi found that viral infections were predominant in children with community acquired pneumonia, while bacterial infections were rare. The WHO markers had low sensitivity in predicting the need for hospitalization, suggesting the need for further research in this area.
Article
Medicine, Research & Experimental
Linan Xu, Fiachra Humphries, Nezira Delagic, Bingwei Wang, Ashling Holland, Kevin S. Edgar, Jose R. Hombrebueno, Donna Beer Stolz, Ewa Oleszycka, Aoife M. Rodgers, Nadezhda Glezeva, Kenneth McDonald, Chris J. Watson, Mark T. Ledwidge, Rebecca J. Ingram, David J. Grieve, Paul N. Moynagh
Summary: The study demonstrated the instability of human ECSIT in a mouse model, with low levels of expression leading to impaired clearance of Salmonella and severe cardiac hypertrophy. Additionally, a reduction in mROS in macrophages was observed.
Article
Cardiac & Cardiovascular Systems
Valentina Cannone, Mark Ledwidge, Chris Watson, Paul M. McKie, John C. Jr Jr Burnett, Kenneth McDonald
Summary: B-type natriuretic peptide (BNP) has blood-pressure-lowering, antifibrotic, and aldosterone-suppressing properties, with genetic variations influencing circulating BNP levels and risk of cardiovascular events. Future studies should investigate the role of BNP genetic testing and BNP-based therapy in heart failure prevention.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2021)
Article
Cardiac & Cardiovascular Systems
Claire Sweeney, Rebabonye B. Pharithi, Brian Kerr, Cristin Ryan, Fiona Ryan, Libhan Collins, Carmel Halley, Matt Barrett, Chris J. Watson, Kenneth McDonald, Mark Ledwidge
Summary: Guidelines support the use of BNP and NT-proBNP for risk stratification in heart failure prevention programs. However, a study in a Caucasian population did not find routine simultaneous measurement of both BNP and NT-proBNP to be warranted for predicting HF or LVD.
Article
Medicine, General & Internal
Dafni K. Plati, Evanthia E. Tripoliti, Aris Bechlioulis, Aidonis Rammos, Iliada Dimou, Lampros Lakkas, Chris Watson, Ken McDonald, Mark Ledwidge, Rebabonye Pharithi, Joe Gallagher, Lampros K. Michalis, Yorgos Goletsis, Katerina K. Naka, Dimitrios I. Fotiadis
Summary: The study effectively addressed chronic heart failure diagnosis using machine learning methods, achieving a high accuracy of 91.23%, sensitivity of 93.83%, and specificity of 89.62% when combining features from all categories.
Article
Radiology, Nuclear Medicine & Medical Imaging
Amy C. O'Brien, Roisin MacDermott, Stephen Keane, David T. Ryan, Niall McVeigh, Rory Durand, Maria Ferre, David J. Murphy, Polakit Teekakirikul, David Keane, Ken McDonald, Mark Ledwidge, Jonathan D. Dodd
Summary: This study evaluated a manual method of measuring cardiac MRI e' as a measure of diastolic dysfunction in patients with hypertrophic cardiomyopathy. The results showed that cardiac MRI e' correlated with LGE and other feature tracking measures of diastolic function. It was also found to be an independent predictor of LGE >= 10% and diastolic dysfunction.
EUROPEAN JOURNAL OF RADIOLOGY
(2022)
Review
Genetics & Heredity
Joseph O'Shea, Mark Ledwidge, Joseph Gallagher, Catherine Keenan, Cristin Ryan
Summary: Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are limited, and a more holistic and integrated approach is needed. Pharmacogenetics has the potential to improve medicines optimisation. Current studies suggest that pharmacist-led medicines optimisation, including pharmacogenetics, could have significant benefits for patients and health systems. However, further studies are needed to establish the generalizability of these findings in real-world patient populations.
PHARMACOGENOMICS JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Laura Murphy, Gerard T. Giblin, Neasa Starr, Norma Caples, Regina Black, Carmel Halley, Kenneth McDonald, Emer Joyce
Summary: This study aimed to identify the accurate prevalence data for ambulatory advanced heart failure (HF) in European countries. The survey results showed that approximately 5% of the all-comer routine HF clinic population could be eligible for referral to an advanced HF center for assessment for advanced surgical therapies. The study also found that almost one-quarter of patients in this chronic outpatient population had NYHA III-IV symptoms. These findings are important for resource and service planning.
Letter
Cardiac & Cardiovascular Systems
[Anonymous]
IJC HEART & VASCULATURE
(2022)
Review
Medicine, General & Internal
Dermot M. Wildes, Master Chisale, Richard J. Drew, Peter Harrington, Chris J. Watson, Mark T. Ledwidge, Joe Gallagher
Summary: The study aimed to identify clinical prediction rules for predicting hospitalization in children with lower respiratory tract infection in primary care. Validation of one model was performed, showing effectiveness in predicting hospitalization due to bacterial infection.
Article
Cardiac & Cardiovascular Systems
Claire Sweeney, Rebabonye B. Pharithi, Brian Kerr, Cristin Ryan, Fiona Ryan, Libhan Collins, Carmel Halley, Matt Barrett, Chris J. Watson, Kenneth McDonald, Mark Ledwidge
Summary: The study found that the NT-proBNP/BNP ratio was inversely associated with the future development of heart failure and left ventricular dysfunction risk. However, the study does not support routine simultaneous measurement of BNP and NT-proBNP in heart failure prevention programs among European, Caucasian patients.