Review
Biochemistry & Molecular Biology
Amirhossein Davoodvandi, Banafsheh Nikfar, Russel J. Reiter, Zatollah Asemi
Summary: Melatonin plays important roles in mammals, regulating circadian rhythms, enhancing immunity, and inhibiting cancer. Epigenetic drugs have gained attention for their potential in cancer treatment. This report summarizes the effects of melatonin on DNA methylation in cancer cells and discusses the impact of artificial light on melatonin secretion and cancer cell DNA methylation.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Eshaan Patnaik, Chikezie Madu, Yi Lu
Summary: Epigenetics plays a crucial role in gene regulation and tumor development. DNA methylation inhibitors and histone deacetylase inhibitors can restore normal gene expression and be effective against cancer. Understanding epigenetic modifications and utilizing inhibitors offer new possibilities for cancer research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Veronica Davalos, Manel Esteller
Summary: Cancer development is caused by changes in the structure and function of the genome. Epigenetic alterations regulate gene expression programs that promote tumorigenesis and can be used as useful tools in clinical decision making. Unlike genetic changes, epigenetic modifications can be reversed, making them an attractive target for drug development.
CA-A CANCER JOURNAL FOR CLINICIANS
(2023)
Review
Biochemistry & Molecular Biology
Sarah S. Wang, Jihao Xu, Keely Y. Ji, Chang-Il Hwang
Summary: Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDA), is a significant cause of cancer-related deaths in the United States. While genetic mutations driving PDA initiation and progression have been identified, the mechanisms underlying PDA metastasis remain elusive. It is suggested that epigenetic fluctuations may play a critical role in driving PDA metastasis.
Review
Cell Biology
Dipanwita Das, Nandini Karthik, Reshma Taneja
Summary: Inflammation is a crucial immune response against infection and tissue damage, but chronic inflammation is linked to cancer development. Immune cells produce inflammatory mediators to facilitate tumor growth, while aberrant expression of inflammatory factors by tumor cells recruits immune cells for mutual crosstalk, creating a conducive environment for tumor growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bernice Sepers, Rebecca Shuhua Chen, Michelle Memelink, Koen J. F. Verhoeven, Kees van Oers
Summary: As environmental fluctuations become more frequent, organisms need to adapt quickly to changes caused by humans, climate, and ecology. Epigenetic modifications, specifically DNA methylation, play a role in shaping a organism's phenotypic responses during development. While studies have shown that environmentally induced DNA methylation changes occur, we have limited understanding of the proportion of the epigenome affected by environmental factors compared to genetic variation. In this study, using a partial cross-foster design in a great tit population, we found that common origin explained the variance in DNA methylation in 8,315 CpG sites while common rearing environment only explained 101 sites. Furthermore, we identified quantitative trait loci for the CpG sites related to brood origin, with 754 cis and 4,202 trans methylation quantitative trait loci involving 24% of the CpG sites. These findings suggest that the influence of environmentally induced methylation marks, independent of genotype, is limited and that genetic factors play a larger role in determining DNA methylation variation early in life.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
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
Biochemistry & Molecular Biology
Xiao Han, Fang Fang, Weiwei Cui, Ya Liu, Yuxin Liu
Summary: This study investigates the effect of alcohol consumption on cervical cancer by examining the methylation status of cervical cancer cells. The results suggest that ethanol can affect the expression of DNMT by inducing methyl donor consumption, leading to genome-wide hypomethylation in cervical cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Environmental Sciences
Rui Yan, Xu-Li Chen, Yan-Ming Xu, Andy T. Y. Lau
Summary: Research has shown that e-cigarette aerosols contain many toxic compounds that can adversely affect the human epigenome. Ingredients in e-cigarettes such as nicotine, volatile organic compounds, etc., can also affect DNA methylation, leading to the development of diseases.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Anshu Agarwal, Vikash Kansal, Humaira Farooqi, Ram Prasad, Vijay Kumar Singh
Summary: Head and neck cancers, particularly head and neck squamous cell carcinoma (HNSCC), are highly lethal and their prognosis is poor. Epigenetic alterations, such as DNA hypermethylation, play a crucial role in HNSCC development. This study investigated the effect of EGCG, a compound found in green tea, on DNA hypermethylation and HNSCC growth. The results showed that EGCG significantly inhibited DNA hypermethylation and reduced the activity and expression of DNA methyltransferases, leading to the reactivation of tumor suppressor genes and decreased cell proliferation in HNSCC cells. In an in vivo study, EGCG supplementation effectively inhibited tumor growth in mice xenografts. Overall, this study highlights the potential of EGCG as a promising therapeutic strategy for HNSCC.
Article
Biochemistry & Molecular Biology
Raul F. Perez, Juan Ramon Tejedor, Pablo Santamarina-Ojeda, Virginia Lopez Martinez, Rocio G. Urdinguio, Lucia Villamanan, Ana Paula Candiota, N. Mi Vidal Sarro, Marta Barradas, Pablo Jose Fernandez-Marcos, Manuel Serrano, Agusin F. Fernandez, Mario F. Fraga
Summary: The study found parallel epigenetic alterations in aging and cancer, with potential differences in DNA hypomethylation. While most observations came from mouse models, systematic comparisons of human and mouse epigenetic patterns in disease context are lacking. The research suggests the conservation of specific cancer and aging epigenomic signatures in human and mouse, indicating the functional consequences of these alterations at multiple levels of genomic regulation.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Review
Oncology
Yuhao Zhao, Mao Yang, Shijia Wang, Sk Jahir Abbas, Junzhe Zhang, Yongsheng Li, Rong Shao, Yingbin Liu
Summary: This review focuses on the mechanistic insights of DNA, histone, and RNA methylation in regulating the progression of pancreatic cancer. The roles of methylation regulators in modulating gene expression associated with cell proliferation, invasion, and apoptosis are discussed. Recent clinical trials on methylation drug targeting are also explored. Understanding the novel regulatory mechanisms of methylation modification may offer alternative opportunities to improve therapeutic efficacy in combating this devastating disease.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Zhenhui Zhong, Suhua Feng, Sascha H. Duttke, Magdalena E. Potok, Yiwei Zhang, Javier Gallego-Bartolom, Wanlu Liu, Steven E. Jacobsen
Summary: DNA methylation influences chromatin accessibility, particularly in heterochromatin, in plants. Different sequence contexts of DNA methylation interact with each other, and methylation can impact chromatin structure through mechanisms other than transcription. Increased chromatin accessibility is associated with enhanced long-range chromatin interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, Research & Experimental
Ningxin Qu, Ting Luan, Naiquan Liu, Chenhui Kong, Le Xu, Hong Yu, Ye Kang, Ye Han
Summary: HNF4 alpha, a transcription factor, plays a vital role in regulating functional genes and biological processes. Aberrant expression of HNF4 alpha is associated with tumor progression and metastasis, potentially by affecting downstream target genes and signaling pathways.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Simeon Santourlidis, Wolfgang A. Schulz, Marcos J. Arauzo-Bravo, Daniela Gerovska, Pauline Ott, Marcelo L. Bendhack, Mohamed Hassan, Lars Erichsen
Summary: Epigenetic mechanisms play a fundamental role in the initiation and development of melanoma, but research in this area is relatively limited compared to other cancers. This review provides a brief summary of the epigenetic aspects relevant to melanoma pathogenesis and introduces new perspectives from epigenetic research in other cancers that may have potential for melanoma diagnosis and therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Respiratory System
Hannelore P. Van Eeckhoutte, Chantal Donovan, Richard Y. Kim, Thomas M. Conlon, Meshal Ansari, Haroon Khan, Ranjith Jayaraman, Nicole G. Hansbro, Yves Dondelinger, Tom Delanghe, Allison M. Beal, Brad Geddes, John Bertin, Tom Vanden Berghe, Joyceline De Volder, Tania Maes, Peter Vandenabeele, Bart M. Vanaudenaerde, Dieter Deforce, Sonja Skevin, Filip Van Nieuwerburgh, Fien M. Verhamme, Guy F. Joos, Sobia Idrees, Herbert B. Schiller, Ali Oender Yildirim, Alen Faiz, Mathieu J. M. Bertrand', Guy G. Brusselle, Philip M. Hansbro, Ken R. Bracke
Summary: RIPK1 plays a key role in COPD pathogenesis by mediating cell death and inflammation. Inhibition of RIPK1 kinase activity can alleviate airway inflammation and cell death caused by COPD, making it a potential therapeutic approach.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Genetics & Heredity
Tamara Jarayseh, Brecht Guillemyn, Hanna De Saffel, Jan Willem Bek, Delfien Syx, Sofie Symoens, Yannick Gansemans, Filip Nieuwerburgh, Sujatha Jagadeesh, Jayarekha Raja, Fransiska Malfait, Paul J. Coucke, Adelbert De Clercq, Andy Willaert
Summary: Bi-allelic mutations in TAPT1 gene lead to a wide range of phenotypes, from severe skeletal and congenital abnormalities to isolated early-onset cataract. A frameshift mutation in the TAPT1 gene was identified in a patient with bilateral early-onset cataract and skeletal abnormalities, expanding the phenotypic spectrum. A zebrafish model with TAPT1 gene knockout exhibited eye malformations, loss of vision, increased photokinetics, and hyperpigmentation, providing insights into the ultrastructural and molecular characteristics of TAPT1 mutations.
Article
Immunology
Kai Ling Liang, Juliette Roels, Marieke Lavaert, Tom Putteman, Lena Boehme, Laurentijn Tilleman, Imke Velghe, Valentina Pegoretti, Inge van de Walle, Stephanie Sontag, Jolien Vandewalle, Bart Vandekerckhove, Georges Leclercq, Pieter Van Vlierberghe, Claude Libert, Filip Van Nieuwerburgh, Roman Fischer, Roland E. Kontermann, Klaus Pfizenmaier, Gina Doody, Martin Zenke, Tom Taghon
Summary: The interaction between thymocytes and thymic stromal cells is crucial for T cell development. This study demonstrates that intrathymic development of dendritic cells (DCs) plays a role in supporting early stages of human T cell development. The transcription factor IRF8 and transmembrane TNF are involved in this process. Selective targeting of TNFR2 has the potential to enhance the generation of T cell precursors for clinical applications.
Review
Oncology
Evie Papavasiliou, Valerie A. Sills, Natalia Calanzani, Hannah Harrison, Claudia Snudden, Erica di Martino, Andy Cowan, Dawnya Behiyat, Rachel Boscott, Sapphire Tan, Jennifer Bovaird, Grant D. Stewart, Fiona M. Walter, Yin Zhou
Summary: Bladder cancer is a common cancer worldwide and early diagnosis is crucial for better survival rates. Urinary biomarkers have been developed but their diagnostic performance in the general population is limited. This study systematically reviewed evidence on biomarkers suitable for use in community and primary care settings, identifying three biomarkers with similar diagnostic performance and some promising novel biomarkers. Further validation studies in the general population are needed.
Article
Oncology
Jennifer Bre, Alison L. Dickson, Oliver J. Read, Ying Zhang, Fiona G. McKissock, Peter Mullen, Peijun Tang, Greice M. Zickuhr, Clarissa M. Czekster, David J. Harrison
Summary: NUC-3373 is a modified version of 5-fluorodeoxyuridine that shows higher anti-cancer activity and better safety profile compared to 5-FU, overcoming its limitations and pharmacologic challenges in clinical use.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Immunology
Lore Billiet, Laurenz De Cock, Guillem Sanchez Sanchez, Rupert L. Mayer, Glenn Goetgeluk, Stijn De Munter, Melissa Pille, Joline Ingels, Hanne Jansen, Karin Weening, Eva Pascal, Killian Raes, Sarah Bonte, Tessa Kerre, Niels Vandamme, Ruth Seurinck, Jana Roels, Marieke Lavaert, Filip Van Nieuwerburgh, Georges Leclercq, Tom Taghon, Francis Impens, Bjorn Menten, David Vermijlen, Bart Vandekerckhove
Summary: Billiet et al. identify a well-defined but heterogeneous unconventional TCR alpha beta(+) lineage mainly confined to CD8(+) Helios(+) T cells, which represents the post-thymic progeny of CD10(+) PD-1(+) precursors in humans. These unconventional T cells (UTCs) in thymus and blood share a common developmental trajectory, characterized by hallmark transcription factors (ZNF683 and IKZF2) and a polycolonal TCR repertoire with autoreactive features. The UTC lineage can be identified in adult blood and intestinal tissues.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Christina Fell, Mahnaz Mohammadi, David Morrison, Ognjen Arandjelovic, Sheeba Syed, Prakash Konanahalli, Sarah Bell, Gareth Bryson, David J. Harrison, David Harris-Birtill
Summary: In this study, AI was used to categorise endometrial biopsy whole slide images into malignant, other, benign, or insufficient categories. The digitalisation of pathology has led to the automation of image analysis, and a model that can classify slides in this way would help prioritise pathologists' workload and reduce diagnosis time for cancer patients. The final model achieved an accuracy of 90% in classifying slides correctly and 97% in the malignant class, demonstrating its effectiveness in assisting pathologists.
Article
Virology
Thomas-Wolf Verdonckt, Anton Bilsen, Filip Van Nieuwerburgh, Loes De Troij, Dulce Santos, Jozef Vanden Broeck
Summary: Insect cell expression systems are used in the medical industry for vaccine development against diseases like COVID-19. The study focuses on the characterization of a specific virus called Bombyx mori latent virus (BmLV) and its pathogenicity. The results demonstrate that a variant of BmLV causes acute infections and strong cytopathic effects in cell lines and animal models. The study also examines the RNAi-based immune response in the cell line and animal models, shedding light on the genomic diversity of BmLV.
Article
Computer Science, Information Systems
Georg Wolflein, In Hwa Um, David J. Harrison, Ognjen Arandjelovic
Summary: In recent years, efforts have been made to digitize whole-slide images of cancer tissue, providing new opportunities for deep learning in oncology. One promising application is virtual staining, where a deep learning model reproduces the appearance of stained tissue sections based on different input stains. However, there is a scarcity of supervised training data with aligned input and output stains on the same tissue sections. In this work, a dataset of ten whole-slide images of clear cell renal cell carcinoma tissue sections, along with over 600,000 patches and cell segmentation masks, is introduced to facilitate the development of deep learning methods for digital pathology and benchmark virtual staining models.
Article
Biochemistry & Molecular Biology
Suneeta Devi, Anna E. Carberry, Greice M. Zickuhr, Alison L. Dickson, David J. Harrison, Rafael G. da Silva
Summary: DNPH1 catalyzes the N-ribosidic bond cleavage of 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate to generate 2-deoxyribose 5-phosphate and 5-hydroxymethyluracil. The crystal structures of unliganded DNPH1 and DNPH1 bound with 2'-deoxyuridine 5'-monophosphate were solved, revealing the interaction between the catalytic Glu residue and a conserved Tyr residue. Functional data supported the proposed mechanism, with hydrolysis of dUMP confirmed by liquid chromatography-mass spectrometry analysis. The pH-rate profile and solvent isotope effects provided insights into the catalytic mechanism.
Article
Multidisciplinary Sciences
A. S. Vermeersch, M. Ali, Y. Gansemans, F. Van Nieuwerburgh, P. Geldhof, R. Ducatelle, D. Deforce, J. Callens, G. Opsomer
Summary: This study is the first to explore the changes in gene expression in severe udder cleft dermatitis lesions (UCD) in Holstein-Friesian cows. RNA Seq-Technology was used to compare gene expression levels in UCD lesions and healthy udder skin, revealing significant differences in inflammatory pathways. Upregulated genes included chemokines CXCL2, CXCL5, CXCL8, and CCL11, as well as multifunctional molecules ADAM12 and SLPI, while downregulated genes were associated with keratins. Pathway analysis showed significant upregulation of inflammatory pathways such as chemokine signaling, cytokine receptor interaction, and IL-17 signaling. These findings suggest a dysregulated inflammatory response, disrupted skin barrier integrity, and impaired wound repair mechanism in severe UCD lesions.
Article
Agriculture, Dairy & Animal Science
Marielen de Souza, Venessa Eeckhaut, Evy Goossens, Richard Ducatelle, Filip Van Nieuwerburgh, Karl Poulsen, Ana Angelita Sampaio Baptista, Ana Paula Frederico Rodrigues Loureiro Bracarense, Filip Van Immerseel
Summary: Galactomannans in broiler feed can negatively impact zootechnical performance and gut microbiota composition. Mannanase supplementation can restore the gut microbiota and improve performance to normal levels.
Article
Computer Science, Artificial Intelligence
Clarisse F. de Vries, Samantha J. Colosimo, Roger T. Staff, Jaroslaw A. Dymiter, Joseph Yearsley, Deirdre Dinneen, Moragh Boyle, David J. Harrison, Lesley A. Anderson, Gerald Lip
Summary: Artificial intelligence (AI) tools may be helpful in breast screening mammography programs, but their generalizability to new settings should be validated. This study assessed the performance of a commercially available breast screening AI algorithm in a specific clinical site using a 3-year dataset. The algorithm's recall rates were high initially but reduced after threshold calibration and were influenced by software upgrades. Validating AI performance and thresholds in new clinical settings is important, and quality assurance systems should ensure consistency.
RADIOLOGY-ARTIFICIAL INTELLIGENCE
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Georg Wolflein, In Hwa Um, David J. Harrison, Ognjen Arandjelovic
Summary: Understanding the presence and density of specific immune cell types is crucial for evaluating a patient's immune response to cancer. However, traditional immunofluorescence staining methods for identifying T cell subtypes are costly, time-consuming, and not commonly used in clinical settings. In this study, we propose a framework that utilizes generative adversarial networks to virtually stain Hoechst images with CD3 and CD8 markers, enabling the identification of T cell subtypes in clear cell renal cell carcinoma. By jointly learning both staining tasks, our method incorporates mutually beneficial information to improve accuracy. We also introduce a novel metric to evaluate the quality of virtual staining.
2023 IEEE/CVF WINTER CONFERENCE ON APPLICATIONS OF COMPUTER VISION (WACV)
(2023)
