Review
Chemistry, Multidisciplinary
Harshita Shet, Rajesh Sahu, Yogesh S. Sanghvi, Anant R. Kapdi
Summary: Fluorinated nucleosides and oligonucleotides are widely used as probes for studying nucleic acid interactions, structures, transformations, and biomedical applications. The unique properties of fluorine atoms, such as small size, electronegativity, lipophilicity, and stereochemical control, have attracted attention for the fluorination of preformed nucleosides and/or nucleotides. This review discusses the synthetic protocols for selective fluorination of sugar or base moieties in preformed nucleosides, nucleotides, and nucleic acids using specific fluorinating reagents.
Article
Chemistry, Inorganic & Nuclear
Joanna Skiba, Aleksandra Kowalczyk, Damian Trzybinski, Krzysztof Wozniak, Valerije Vrcek, Magdalena Gapinska, Konrad Kowalski
Summary: This paper reports a Yb(OTf)(3)-mediated etherification reaction to obtain R,R and S,R isomers of ferrocenyl glycol nucleic acid (Fc-GNA) nucleosides from their stereo-defined (S,R) precursor. The mechanism of the reaction is explained by density functional theory calculations, and the obtained compounds show reversible oxidation of the ferrocenyl portion. Anticancer activity studies reveal that the (S,R) nucleoside exhibits the highest activity against cancer cells HeLa and Ishikawa, inducing apoptosis in HeLa cells at a concentration of IC50=66.0 μM after 72 hours of treatment.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Joern Bargstedt, Martin Reinschmidt, Leon Tydecks, Theresa Kolmar, Christoph M. Hendrich, Andres Jaeschke
Summary: Photochromic nucleosides have emerged as a promising approach for manipulating and studying complex processes in living organisms. This review highlights recent advancements in this field, including design principles, synthetic strategies, analytical challenges, and applications. The incorporation of photoswitchable moieties into biological macromolecules allows for light-responsive behavior, offering advantages in cellular and tissue applications due to its non-invasive nature. This field holds great potential for precise control of gene expression and modulation of biomolecular structure and function.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Mathijs J. Pals, Willem A. Velema
Summary: Terminal deoxynucleotidyl Transferase (TdT) is a template-independent DNA polymerase that has gained interest as a leukemia biomarker and potential therapeutic target. A FRET-quenched fluorogenic probe based on a size-expanded deoxyadenosine was developed to directly report on TdT enzymatic activity. The probe showed selectivity over other enzymes and its activity could be monitored in human T-lymphocyte cell extract and Jurkat cells using a simple fluorescence assay. A non-nucleoside TdT inhibitor was identified using the probe in a high-throughput assay.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Nanoscience & Nanotechnology
Cui Tang, Hui Wang, Lina Guo, Chan Zou, Jianming Hu, Hanyong Zhang, Wenhu Zhou, Guoping Yang
Summary: Atherosclerosis (AS) is a major contributor to cardiovascular diseases, and novel therapeutic strategies are needed to alleviate plaque burden. This study found that CpG can enhance macrophage efferocytosis and promote plaque regression. CpG conjugated on silver nanoparticles (CpG-AgNPs) showed excellent therapeutic efficacy and biocompatibility.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Organic
Misa Shoji, Yasufumi Fuchi, Takashi Osawa, Han Kim, Yuta Ito, Yoshiyuki Hari
Summary: In this study, a unique consecutive three-acetal-containing nucleic acid (TaNA) was designed and its methylated derivatives were synthesized. The modified oligonucleotides showed higher stability when forming duplexes or triplexes compared to natural and other modified oligonucleotides, and also exhibited enhanced nuclease resistance.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Takayuki Kanagawa, Shigetoshi Tachibana, Yoshiaki Masaki, Kohji Seio
Summary: A cyclic nucleoside has been designed and synthesized to introduce specific conformations into functional nucleic acids by fixing the rotation, base orientation, and sugar structure.
Review
Biochemistry & Molecular Biology
Anna Davydova, Yuliya Kurochkina, Veronika Goncharova, Mariya Vorobyeva, Maksim Korolev
Summary: Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic diseases that primarily affect the spinal and sacroiliac joints. The pathogenesis of SpA involves the overproduction of proinflammatory cytokines, particularly IL-17A. Targeted anti-IL17 therapies have proven to be the most effective treatment for SpA.
Review
Food Science & Technology
Ting Ding, Ge Song, Xinran Liu, Meihong Xu, Yong Li
Summary: Nucleotides are the basic units of nucleic acid macromolecules, playing important physiological and biochemical functions in organisms. Recent studies have shown that exogenous nucleotides are essential nutrients under specific physiological conditions, entering tissues, reducing the body's synthesis needs, and enhancing immune function and regulating intestinal flora.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Physics, Fluids & Plasmas
Qiujin Wang, Shuo Lin, Xuan Liu, Wen Xu, Yiming Xiao, Changneng Liang, Lan Ding, F. M. Peeters
Summary: This study experimentally investigated the photoluminescence properties of DNA under different optical excitations, revealing that the behavior of ssDNA can be classified into two categories depending on the excitation wavelength. Different transition channels exist for different excitation wavelengths, while the strand length and base type also have an impact on the photoluminescence properties.
Article
Chemistry, Multidisciplinary
Qiang Li, Marko Trajkovski, Chaochao Fan, Jialiang Chen, Yifei Zhou, Kuan Lu, Hongjun Li, Xuncheng Su, Zhen Xi, Janez Plavec, Chuanzheng Zhou
Summary: Fluorinated nucleotides are crucial for F-19 NMR studies of nucleic acid structure and function. The synthesized 4'-SCF3-thymidine exhibits high adaptability and sensitivity, making it valuable for distinguishing diverse DNA structures with single-nucleotide resolution.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Thorben Frohlking, Mattia Bernetti, Giovanni Bussi
Summary: This paper presents a novel method that combines the maximum entropy principle, the Bayesian-inference of ensembles approach, and the optimization of empirical forward models. The method has been applied to study the Karplus parameters for RNA systems, achieving good agreement between simulations and experiments by correcting errors in the forward models and reweighting the sampled structural dynamics.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Hui Yang, Elena Eremeeva, Mikhail Abramov, Piet Herdewijn
Summary: The study demonstrates that modified nucleic acid fragments can be transcribed into natural or modified RNA and serve as genetic templates in vivo for encoding target proteins, showcasing the potential of synthetic materials in genetics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Nutrition & Dietetics
Vivek Puri, Manju Nagpal, Inderbir Singh, Manjinder Singh, Gitika Arora Dhingra, Kampanart Huanbutta, Divya Dheer, Ameya Sharma, Tanikan Sangnim
Summary: Nutraceuticals, the nourishing components with nutritional benefits and therapeutic effects, play a significant role in human health care and future therapeutic development. This article discusses the applications of nutraceuticals in health promotion, disease reduction, and support therapy. Nanotechnology can improve the health benefits of nutraceuticals, and prior knowledge of their interactions with drugs helps prevent side effects.
Article
Chemistry, Organic
Yasufumi Fuchi, Kouki Watanabe, Misa Shoji, Yuta Ito, Yoshiyuki Hari
Summary: The pyrimidine derivatives of methylated 2'-O,4'-C-methyleneoxy-bridged nucleic acid (Me-TaNA), a unique consecutive three-acetal-containing nucleic acid, have been shown to be promising building blocks for chemically modified oligonucleotides. In this study, purine derivatives of Me-TaNA (Me-TaNA-A and -G) were synthesized and introduced into oligonucleotides. The modified oligonucleotides, including purine derivatives of Me-TaNA, exhibited increased duplex stability compared to natural oligonucleotides when forming duplexes with single-stranded RNA.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Cardiac & Cardiovascular Systems
Fabian Philipp Kreutzer, Anna Meinecke, Kevin Schmidt, Jan Fiedler, Thomas Thum
Summary: An efficient and safe drug development process plays a crucial role in improving patients' quality of life and lifespan. This article provides an overview of recent technological advances in the field of cardiovascular drug development and suggests improvements to enhance preclinical and clinical drug development. It discusses the advantages and disadvantages of animal experimentation and explores alternative methods such as three-dimensional cell culture, spheroids, and organoids. The potential of microfluidic devices as organ-on-a-chip systems and the use of living animal and human cardiac tissues are also introduced. The article further examines recent randomized clinical trials and proposes modifications to increase lead candidate throughput. In addition, it explores the potential of in silico and N-of-1 trials to redefine the evaluation of clinical drug candidates. Finally, it briefly discusses clinical trial designs during pandemic times.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Fotios G. Pitoulis, Raquel Nunez-Toldra, Ke Xiao, Worrapong Kit-Anan, Saskia Mitzka, Richard J. Jabbour, Sian E. Harding, Filippo Perbellini, Thomas Thum, Pieter P. de Tombe, Cesare M. Terracciano
Summary: We developed a novel methodology to study chronic load in vitro by using a bioreactor that can recreate the electromechanical events of in vivo pressure-volume loops. Rat living myocardial slices (LMS) were cultured for 3 days with the bioreactor to simulate physiological load, pressure-overload, or volume-overload. The results showed that both pressure- and volume-overloaded LMS exhibited decreased contractility, with volume-overload showing more pronounced effects. Cardiomyocyte hypertrophy and dysregulation of signaling pathways were also observed.
CARDIOVASCULAR RESEARCH
(2022)
Review
Cardiac & Cardiovascular Systems
Emma L. Robinson, Andrew H. Baker, Mairi Brittan, Ian McCracken, G. Condorelli, C. Emanueli, P. K. Srivastava, C. Gaetano, T. Thum, M. Vanhaverbeke, C. Angione, S. Heymans, Y. Devaux, T. Pedrazzini, F. Martelli
Summary: This review discusses the challenges in studying the role and regulation of the non-coding transcriptome in cardiovascular disease, including poor annotation of the non-coding genome, determination of transcript cellular distribution, assessment of RNA processing, and identification of cell-type specific changes. It highlights similarities and differences in analyzing the non-coding and protein-coding transcriptomes, as well as the impact of lack of consensus and standardized methods on reproducibility of data.
CARDIOVASCULAR RESEARCH
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Catherine A. Makarewich, Thomas Thum
Editorial Material
Cardiac & Cardiovascular Systems
Thomas Thum
EUROPEAN HEART JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Dongchao Lu, Shambhabi Chatterjee, Ke Xiao, Isabelle Riedel, Cheng-Kai Huang, Alessia Costa, Sarah Cushman, Dimyana Neufeldt, Laura Rode, Arne Schmidt, Malte Juchem, Julia Leonardy, Gwen Buechler, Jonas Blume, Olivia-Luise Gern, Ulrich Kalinke, Wilson Lek Wen Tan, Roger Foo, Aryan Vink, Linda W. van Laake, Peter van der Meer, Christian Baer, Thomas Thum
Summary: This study identified a circular RNA called Circ-INSR, which is down-regulated during cardiac toxicity and remodeling. The researchers found that overexpression of Circ-INSR can prevent and reverse doxorubicin-induced cardiomyocyte death, and improve cardiac function.
EUROPEAN HEART JOURNAL
(2022)
Review
Cardiac & Cardiovascular Systems
Elisa Mohr, Thomas Thum, Christian Baer
Summary: In vitro modeling of the heart is a challenging task in cardiovascular research. Three-dimensional cultivation methods have emerged as a solution to overcome the limitations of traditional two-dimensional cultivation. These methods aim to study the fundamental features of the heart and have great potential in disease research, drug screening, and regenerative therapy. However, there is a need for continuous improvement and adaptation to address limitations such as cardiomyocyte maturation and vascularization.
EUROPEAN JOURNAL OF HEART FAILURE
(2022)
Review
Cardiac & Cardiovascular Systems
Timothy A. McKinsey, Roger Foo, Chukwuemeka George Anene-Nzelu, Joshua G. Travers, Ronald J. Vagnozzi, Natalie Weber, Thomas Thum
Summary: Cardiovascular diseases and heart failure have a significant impact on global health and impose a large economic burden. Despite advances in standard care, the risks for death and readmission of heart failure patients are still unacceptably high, necessitating the development of new therapeutic strategies. This review summarizes current knowledge on novel cellular and epigenetic therapies, with a focus on non-coding RNA-based strategies in early clinical development to counteract cardiac remodeling and heart failure. The review also discusses the current status, limitations, and future perspectives of translating these novel therapies into clinical practice.
CARDIOVASCULAR RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Liam S. Couch, Keith Channon, Thomas Thum
Summary: In this article, the available literature is summarized to focus on the molecular basis for the pathophysiology of TTS, aiming to advance the understanding of this condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
F. J. G. Waleczek, M. Sansonetti, K. Xiao, M. Jung, S. Mitzka, A. Dendorfer, N. Weber, F. Perbellini, T. Thum
Summary: Resident cardiac macrophages (rcMACs) exhibit plasticity and activation in response to changes in the microenvironment, which is essential for in vitro experimentation. The ex vivo model of living myocardial slices (LMS) provides a tool to investigate rcMACs response to immunomodulatory and mechanical stimulations without the interference of other cells. The study identified potential marker genes for inflammation in rcMACs and microRNAs associated with transcriptomic changes, contributing to the understanding of load-triggered cardiac inflammation.
BASIC RESEARCH IN CARDIOLOGY
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Thomas Thum, Carolyn S. P. Lam
CARDIOVASCULAR RESEARCH
(2023)
Review
Cardiac & Cardiovascular Systems
Dimyana Neufeldt, Sarah Cushman, Christian Baer, Thomas Thum
Summary: Considerable progress has been made in managing cancer, but the discovery of previously unknown adverse events poses challenges to treatment. The close relationship between cardiovascular diseases and cancer underscores the need for interdisciplinary study. Non-coding RNAs, particularly circular RNAs, are emerging as potential targets for the simultaneous treatment of cardiac dysfunction and cancer in the field of cardio-oncology.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dominika Lukovic, Ena Hasimbegovic, Johannes Winkler, Julia Mester-Tonczar, Katrin Mueller-Zlabinger, Emilie Han, Andreas Spannbauer, Denise Traxler-Weidenauer, Jutta Bergler-Klein, Noemi Pavo, Georg Goliasch, Sandor Batkai, Thomas Thum, Faiez Zannad, Mariann Gyoengyoesi
Summary: We have designed translational animal models to investigate cardiac profibrotic gene signatures. RNA-seq analysis revealed a clear distinction between the transcriptomes of different myocardial fibrosis (MF) models. Our study identified different gene targets involved in the development of distinct preclinical MF protocols enabling tailoring expression signature-based approach for the treatment of MF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michiaki Nagai, Sergey Shityakov, Manuel Smetak, Hannah Jill Hunkler, Christian Baer, Nicolas Schlegel, Thomas Thum, Carola Yvette Foerster
Summary: Takotsubo syndrome (TTS), characterized by transient wall motion abnormalities of the left ventricle, presents challenges in diagnosis. A comprehensive blood analysis of TTS patients revealed differences in proinflammatory cytokine expression patterns and receptor expression levels. Surprisingly, catecholamine levels in TTS patients were significantly lower than experimentally induced TTS in animals, and exposure to these lower levels did not damage endothelial cells or cardiomyocytes in vitro. Computational analysis identified blood markers and microRNAs associated with TTS development and inflammation. In addition to known risk factors, inflammaging-related pathways were found to contribute to TTS.
Article
Physiology
Alfredo Jesus Lopez-Davila, Natalie Weber, Arnab Nayak, Leon Fritz, Kian Rami Moustafa, Luis Vincens Gand, Enke Wehry, Theresia Kraft, Thomas Thum, Julian Fernandez, Jose Maria Gutierrez, Bruno Lomonte
Summary: Myonecrosis is a clinical manifestation of snake envenomings caused by Viperidae snakes. The toxic actions of certain enzymes on skeletal muscle fibers lead to rapid hypercontraction and cell membrane damage. This study found that these toxins have indirect effects on the contractile machinery of muscle fibers, as they did not directly affect the main parameters of force development in skinned fibers.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)