Article
Neurosciences
Gerardo Ramirez-Mejia, Elvi Gil-Lievana, Oscar Urrego-Morales, Ernesto Soto-Reyes, Federico Bermudez-Rattoni
Summary: The research demonstrates that inhibiting class I HDAC enhances long-term object recognition memory consolidation, coinciding with a peak of BDNF expression 4 hours after acquisition. Blocking the tyrosine kinase B (TrkB) receptor at 4 hours, but not at 8 hours, impairs ORM consolidation.
Article
Oncology
Husvinee Sundaramurthi, Sandra Garcia-Mulero, Valentina Tonelotto, Kayleigh Slater, Simone Marcone, Josep M. Piulats, Ronald William Watson, Desmond J. Tobin, Lasse D. Jensen, Breandan N. Kennedy
Summary: The drug ACY-1215 has been found to inhibit the growth of primary ocular uveal melanoma (UM) cells and UM cells that have spread to the liver, offering potential as a treatment for advanced UM.
Article
Dermatology
Lina Song, Anne Catherine Bretz, Jan Gravemeyer, Ivelina Spassova, Shakhlo Muminova, Thilo Gambichler, Ashwin Sriram, Soldano Ferrone, Juergen C. Becker
Summary: Merkel cell carcinoma is a rare and highly aggressive skin cancer, with immune modulation by immune checkpoint inhibitors showing promise. However, resistance to immunotherapy remains a significant challenge. Histone deacetylase inhibitors like domatinostat have shown potential to reverse low MHC I expression and increase MCC cells' susceptibility to cytotoxic T cell recognition and elimination.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Chemistry, Medicinal
Negar Omidkhah, Razieh Ghodsi
Summary: NO-HDAC dual inhibitors have demonstrated satisfactory therapeutic effects in various diseases and possess high therapeutic potential.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jie Wang, Zhuoxian Cao, Fang Wang, Pan Wang, Jianxiong An, Xiaozhong Fu, Ting Liu, Yan Li, Yongjun Li, Yonglong Zhao, Hening Lin, Bin He
Summary: The study discusses the rational design, synthesis, biological evaluation, molecular docking, and in vivo efficacy study of a class of HDAC inhibitors using N-acetyl lysine mimics derived from cysteine. These inhibitors demonstrated potent HDAC inhibition and broad cytotoxicity against several cancer cell lines, and compound 13d showed significant tumor growth inhibition in a A549 xenograft mice model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Benjamin R. Gilbert, Zane R. Thornburg, Troy A. Brier, Jan A. Stevens, Fabian Grunewald, John E. Stone, Siewert J. Marrink, Zaida Luthey-Schulten
Summary: To model the replication and inheritance of genetic material in cells, researchers created a computational framework that simulates the replication of bacterial chromosomes and applied it to a genetically minimal bacterium. By modeling the chromosome as a self-avoiding polymer and studying its interaction with ribosomes, they found that the mechanisms of loop extrusion and protein complexes are sufficient for chromosome segregation. Additionally, they developed a methodology to validate their cell state predictions by mapping the polymer model to a coarse-grained representation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Wenzhong Yan, Lijun Ling, Yiran Wu, Kexin Yang, Ruiquan Liu, Jinfeng Zhang, Simeng Zhao, Guisheng Zhong, Suwen Zhao, Hualiang Jiang, Chengying Xie, Jianjun Cheng
Summary: Adenosine serves as an immunosuppressive factor in the tumor microenvironment by activating the A(2A) adenosine receptor. Dual-acting compounds targeting A(2A)R and HDAC are potentially effective immunotherapeutic agents that show promising antitumor activity in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Weifen Li, Tahir Ali, Shengnan Mou, Qichao Gong, Ningning Li, Liangliang Hao, Zhi-Jian Yu, Shupeng Li
Summary: Dopamine and serotonin signaling are associated with major depressive disorder, and targeting their signaling pathway is crucial for improving depression treatment. A study found that serotonin receptor 2A (5-HT2AR) abundantly forms a protein complex with dopamine receptor 1 (D1R), which regulates synaptic regulation through CREB/ERK/AKT modulation and affects depressive symptoms.
Article
Biochemistry & Molecular Biology
Hsueh-Yun Lee, Di-Wei Tang, Chi-Yuan Liu, Er-Chieh Cho
Summary: This study focuses on the development of benzamide-based compounds as potential HDAC1/2 inhibitors for colorectal cancer treatment. Compound 9 is identified as a selective HDAC inhibitor with significant anticancer activity against colorectal cancer cells. The study also investigates the molecular regulatory mechanisms of compound 9, demonstrating its potential in apoptosis activation, cell cycle arrest induction, DNA damage facilitation, and cancer migration suppression in colorectal cancer cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Fangyuan Cao, Zhangping Xiao, Siwei Chen, Chunlong Zhao, Deng Chen, Hidde J. Haisma, Frank J. Dekker
Summary: A novel dual inhibitor targeting HDAC and MIF was found to be toxic to EGFR mutated NSCLC cells, enhancing TKI efficacy and overcoming therapy resistance.
BIOORGANIC CHEMISTRY
(2021)
Article
Immunology
Jinni Wang, Ning Su, Yu Fang, Shuyun Ma, Yuchen Zhang, Jun Cai, Qihua Zou, Xiaopeng Tian, Yi Xia, Panpan Liu, Zhiming Li, He Huang, Huiqiang Huang, Qingqing Cai
Summary: This study compared the benefit of chidamide combined with traditional chemotherapy against newly diagnosed PTCL with traditional chemotherapy alone. Prognostic factors related to progression and survival in patients with untreated PTCL were also investigated. The results showed that the combination of chidamide and chemotherapy resulted in a better progression-free survival compared to chemotherapy alone, especially in patients with high IPI scores. However, there was no significant difference in overall survival between the two groups.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Endocrinology & Metabolism
Jingru Yang, Cong Song, Xianquan Zhan
Summary: Protein acetylation is an important molecular event that is involved in various biological processes, including carcinogenesis. The modulation of protein acetylation levels can lead to the discovery of therapeutic drugs and lay the foundation for precision medicine in oncology.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Medicinal
Zhijie Wang, Donglin Wu, Xiaofei Zhao, Canlin Liu, Siming Jia, Qindi He, Fei Huang, Zitian Cheng, Tao Lu, Yadong Chen, Yun Chen, Pei Yang, Shuai Lu
Summary: AML patients need new therapies due to poor outcomes and relapse with single-target drugs. Inhibiting multiple oncogenic signals simultaneously is a promising strategy. This study developed novel dual FLT3/HDAC inhibitors through rational drug design and demonstrated their potential for AML treatment. The inhibitors blocked FLT3 and HDAC pathways, induced apoptosis, and arrested cell cycle.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ying-Chao Duan, Lin-Feng Jin, Hong-Mei Ren, Shao-Jie Zhang, Yue-Jiao Liu, Yong-Tao Xu, Zi-Hao He, Yu Song, Hang Yuan, Shu-Hui Chen, Yuan-Yuan Guan
Summary: LSD1 and HDAC are closely related in various human cancers, and simultaneous pharmacological inhibition of them can have synergistic anti-cancer effects. Novel LSD1/HDAC bifunctional inhibitors were designed and synthesized, with compounds 5d and 5m showing potent anti-cancer activities and selectivity against other enzymes. Compound 5m, in particular, demonstrated superior in vitro anticancer potency against gastric cancer cell lines compared to existing drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Ting He, Yinglei Gao, Yanfen Fang, Yangming Zhang, Shuwei Zhang, Fajun Nan, Jian Ding, Yi Chen
Summary: This study found that GCJ-490A effectively inhibited the proliferation of NSCLC cells and induced apoptosis both in vitro and in vivo. Furthermore, GCJ-490A increased histone acetylation at the IKK?? promoter by inhibiting HDAC1 and HDAC6, resulting in the downregulation of c-Met. This downregulation was essential for the synergistic anti-tumor activity of GCJ-490A and gefitinib. These findings provide a potential strategy for NSCLC treatment by using HDAC inhibitors in combination with EGFR inhibitors.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Cell Biology
Laura Tamberg, Mariliis Jaago, Kristi Saalik, Alex Sirp, Jurgen Tuvikene, Anastassia Shubina, Carl Sander Kiir, Kaja Nurm, Mari Sepp, Tonis Timmusk, Mari Palgi
DISEASE MODELS & MECHANISMS
(2020)
Article
Biology
Jurgen Tuvikene, Eli-Eelika Esvald, Annika Rahni, Kaie Uustalu, Anna Zhuravskaya, Annela Avarlaid, Eugene Makeyev, Tonis Timmusk
Summary: An intronic enhancer region inside the Bdnf gene has been identified to regulate the expression of Bdnf transcripts in neurons, with a functional E-box element linking Bdnf expression to various pro-neural basic helix-loop-helix transcription factors. These findings shed new light on the cell-type- and stimulus-specific regulation of the important neurotrophic factor BDNF.
Article
Nutrition & Dietetics
Mariliis Jaago, Uku Siim Timmusk, Tonis Timmusk, Kaia Palm
Summary: This study investigated the effects of nutritional supplements on the gut microbiome composition of an athlete, showing significant changes in microbial diversity and composition with fiber intake. The research expands understanding of how dietary fiber supplements can support high energy needs in intensive sports like rowing.
FRONTIERS IN NUTRITION
(2021)
Article
Multidisciplinary Sciences
Ioannis Sarropoulos, Mari Sepp, Robert Fromel, Kevin Leiss, Nils Trost, Evgeny Leushkin, Konstantin Okonechnikov, Piyush Joshi, Peter Giere, Lena M. Kutscher, Margarida Cardoso-Moreira, Stefan M. Pfister, Henrik Kaessmann
Summary: This study investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood using snATAC-seq profiles. The research revealed spatiotemporal heterogeneity among progenitor cells and gradual divergence in the regulatory programs of cerebellar neurons during differentiation. Comparison to vertebrate genomes showed a shared decrease in CRE conservation during development and differentiation, as well as differences in constraint between cell types. The study provides insights into mammalian organ development dynamics and evolutionary gene regulation in cerebellar cells.
Article
Neurosciences
Kaja Nurm, Mari Sepp, Carla Castany-Pladevall, Jordi Creus-Muncunill, Jurgen Tuvikene, Alex Sirp, Hanna Vihma, Derek J. Blake, Esther Perez-Navarro, Tonis Timmusk
Summary: Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by motor symptoms appearing in midlife, and research suggests that isoform-specific changes in TCF4 expression in HD may contribute to progressive impairment of transcriptional regulation and neuronal function in the disease.
Article
Biochemistry & Molecular Biology
Alex Sirp, Kaisa Roots, Kaja Nurm, Juergen Tuvikene, Mari Sepp, Tonis Timmusk
Summary: Transcription factor 4 (TCF4) is a crucial factor for neurocognitive development, and mutations in TCF4 are associated with various neuro-developmental disorders. This study found that missense mutations in TCF4 can impact the protein's DNA-binding and transcriptional activity, with effects depending on cell type, TCF4 isoform, and dimerization partner. Context plays a key role in determining the outcomes of TCF4 mutations.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Neurosciences
Eli-Eelika Esvald, Jurgen Tuvikene, Andra Moistus, Kathy Rannaste, Susann Koomagi, Tonis Timmusk
Summary: In this study, the regulation of BDNF expression in different brain regions was investigated using neuronal populations from rat cerebral cortices and hippocampi. It was found that the expression of BDNF is region-specific and depends on different transcription factors. Additionally, several neurodevelopmentally important transcription factors were identified as brain region-specific regulators of BDNF expression.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ingrid Lekk, Florencia Cabrera-Cabrera, Giorgio Turconi, Jurgen Tuvikene, Eli-Eelika Esvald, Annika Rahni, Laoise Casserly, Daniel R. Garton, Jaan-Olle Andressoo, Tonis Timmusk, Indrek Koppel
Summary: Brain-derived neurotrophic factor (BDNF) promotes neuronal survival and growth during development and is important for synaptic function in the adult nervous system. The Bdnf gene comprises alternative untranslated 5' exons and 3' UTR variants, and the effects of these UTRs on translation have not been established.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Florent Murat, Noe Mbengue, Sofia Boeg Winge, Timo Trefzer, Evgeny Leushkin, Mari Sepp, Margarida Cardoso-Moreira, Julia Schmidt, Celine Schneider, Katharina Moessinger, Thoomke Bruening, Francesco Lamanna, Meritxell Riera Belles, Christian Conrad, Ivanela Kondova, Ronald Bontrop, Ruediger Behr, Philipp Khaitovich, Svante Paeaebo, Tomas Marques-Bonet, Frank Gruetzner, Kristian Almstrup, Mikkel Heide Schierup, Henrik Kaessmann
Summary: Through evolutionary analysis of single-nucleus transcriptome data from 11 species, it was found that the rapid evolution of the testis was driven by accelerated fixation rates of gene expression changes, amino acid substitutions, and new genes in late spermatogenic stages. The study also revealed that genes predominantly expressed in spermatogonia and Sertoli cells accumulated on X chromosomes during evolution, possibly due to male-beneficial selective forces. Additionally, it was discovered that meiotic sex-chromosome inactivation (MSCI) is an ancestral feature in mammalian sex-chromosome systems, including monotremes.
Article
Oncology
Konstantin Okonechnikov, Piyush Joshi, Mari Sepp, Kevin Leiss, Ioannis Sarropoulos, Florent Murat, Martin Sill, Pengbo Beck, Kenneth Chun-Ho Chan, Andrey Korshunov, Felix Sah, Maximilian Y. Deng, Dominik Sturm, John DeSisto, Andrew M. Donson, Nicholas K. Foreman, Adam L. Green, Giles Robinson, Brent A. Orr, Qingsong Gao, Emily Darrow, Jennifer L. Hadley, Paul A. Northcott, Johannes Gojo, Daisuke Kawauchi, Volker Hovestadt, Mariella G. Filbin, Andreas von Deimling, Marc Zuckermann, Kristian W. Pajtler, Marcel Kool, David T. W. Jones, Natalie Jaeger, Lena M. Kutscher, Henrik Kaessmann, Stefan M. Pfister
Summary: This study successfully identified the cellular origins of the three most common pediatric brain tumors and identified potential therapeutic targets based on the tumor-specific genes expressed in these cellular origins.
Article
Ecology
Francesco Lamanna, Francisca Hervas-Sotomayor, A. Phillip Oel, David Jandzik, Daniel Sobrido-Camean, Gabriel N. Santos-Duran, Megan L. Martik, Jan Stundl, Stephen A. Green, Thoomke Bruening, Katharina Moessinger, Julia Schmidt, Celine Schneider, Mari Sepp, Florent Murat, Jeramiah J. Smith, Marianne E. Bronner, Maria Celina Rodicio, Anton Barreiro-Iglesias, Daniel M. Medeiros, Detlev Arendt, Henrik Kaessmann
Summary: By studying the sea lamprey, researchers have created a comprehensive cell type atlas of the primitive vertebrate brain, which has revealed the cellular and molecular architecture of the ancestral vertebrate brain and identified key tissues and cell types that arose later in evolution.
NATURE ECOLOGY & EVOLUTION
(2023)
Article
Medicine, Research & Experimental
Annika Rahni, Mariliis Jaago, Helle Sadam, Nadezda Pupina, Arno Pihlak, Jurgen Tuvikene, Margus Annuk, Andrus Magi, Tonis Timmusk, Amir M. Ghaemmaghami, Kaia Palm
Summary: This study used phage display mimotope variation analysis to profile antibody response in cancer patients receiving immunotherapy. The findings provide insights into the differences and similarities in tumor-specific immunogenicity related to targeted immune treatments, and suggest that antibody epitopes can be used as biomarkers to predict anti-cancer immunity elicited by immunotherapy.
COMMUNICATIONS MEDICINE
(2022)