Article
Chemistry, Medicinal
Chen Chen, Hongrui Chu, Anyang Wang, Huanhuan Yin, Yanqiao Gao, Shuhua Liu, Wei Li, Leiqiang Han
Summary: Incorporating a DNA-binding fragment in HDAC inhibitors has been proven effective in treating hematologic malignancies. However, these inhibitors have poor effects on solid tumors. In this study, a series of 2,5-diphenyl-1,3,4-thiadiazole hydroxamate derivatives were designed and synthesized as HDAC inhibitors with DNA binding affinity. Among them, compound 4j showed the strongest inhibitory activity against HDAC1 and demonstrated potent antiproliferative activity in tumor cell lines. Additionally, compound 4j enhanced the acetylation of histone H3 and alpha-tubulin, as well as activated caspase 3 in HCT116 and MC38 cell lines, leading to significant suppression of tumor growth in the MC38 tumor model. This work validates compound 4j as a promising lead compound for further optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Tianbao Zhu, Xi Chen, Chenglan Li, Jie Tu, Na Liu, Defeng Xu, Chunquan Sheng
Summary: In this study, novel CYP51/HDAC dual inhibitors were designed to show potent antifungal activity against Cryptococcus neoformans and Candida tropicalis infections, by inhibiting various virulence factors and down-regulating resistance-associated genes. This highlights the potential of CYP51/HDAC dual inhibitors as a promising strategy for the discovery of novel broad-spectrum antifungal agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Ji Hye Shin, Min Ji Song, Ji Hyun Kim
Summary: This study examined the effect of valproate (VPA) on brain volume in patients with idiopathic generalized epilepsy. The results showed that patients taking VPA had significant gray matter volume reduction in various brain regions compared to the control group. This finding suggests that the use of VPA may lead to brain volume reductions in certain regions.
Review
Biochemistry & Molecular Biology
Maria Gkotzamanidou, Elisavet Terpou, Nikolaos Kentepozidis, Evangelos Terpos
Summary: Multiple myeloma is characterized by genomic instability and epigenetic regulation, which play important roles in its pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Andrea Lauria, Guohua Meng, Valentina Proserpio, Stefania Rapelli, Mara Maldotti, Isabelle Laurence Polignano, Francesca Anselmi, Danny Incarnato, Anna Krepelova, Daniela Donna, Chiara Levra Levron, Giacomo Donati, Ivan Molineris, Francesco Neri, Salvatore Oliviero
Summary: The establishment of DNA methylation patterns during mouse early development is crucial for cell fate determination. However, the specific molecular targets and mechanisms of de novo methylation machinery during differentiation are not fully understood. In this study, the researchers identified DNMT3B-dependent regulatory elements that play a critical role in cell fate determination. They found that DNMT3B-dependent DNA methylation is essential for proper differentiation and lineage determination, and ectopic expression of DNMT3B can restore normal gene expression and cell fate. This study provides important insights into the role of DNA methylation in early development and cell fate determination.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Viridiana Navarrete-Yanez, Alejandra Garate-Carrillo, Marcos Ayala, Antonio Rodriguez-Castaneda, Patricia Mendoza-Lorenzo, Guillermo Ceballos, Rosa Ordonez-Razo, Sundeep Dugar, George Schreiner, Francisco Villarreal, Israel Ramirez-Sanchez
Summary: The study demonstrated the stimulating effects of both (-)-Epi and (+)-Epi on neuronal proliferation markers, leading to improvements in capillary formation, memory, and neurofilament functions. Additionally, (+)-Epi showed more effective results in upregulating neurogenesis markers compared to (-)-Epi.
Article
Multidisciplinary Sciences
Nora L. Benavidez, Michael S. Bienkowski, Muye Zhu, Luis H. Garcia, Marina Fayzullina, Lei Gao, Ian Bowman, Lin Gou, Neda Khanjani, Kaelan R. Cotter, Laura Korobkova, Marlene Becerra, Chunru Cao, Monica Y. Song, Bin Zhang, Seita Yamashita, Amanda J. Tugangui, Brian Zingg, Kasey Rose, Darrick Lo, Nicholas N. Foster, Tyler Boesen, Hyun-Seung Mun, Sarvia Aquino, Ian R. Wickersham, Giorgio A. Ascoli, Houri Hintiryan, Hong-Wei Dong
Summary: This study provides a comprehensive understanding of how the superior colliculus (SC) receives diverse cortical inputs to drive a variety of behaviors. By mapping cortico-tectal projections, the authors identified distinct zones within the SC and characterized the connectivity and morphology of neurons in each zone, shedding light on the role of SC in goal-directed behaviors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Thibaut Burg, Elisabeth Rossaert, Matthieu Moisse, Philip Van Damme, Ludo Van den Bosch
Summary: Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disorder of the motor system, with defects in metabolism contributing significantly to disease progression. Inhibition of histone deacetylase (HDAC) has been shown to restore metabolic alterations and mitigate lipid homeostasis defects in ALS, suggesting a potential new therapeutic strategy for modulating lipid metabolism in ALS and potentially other neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Shengjie Li, Die Peng, Ni Pan, Shaohui Wang, Zheng Zhang, Cuihong Wan
Summary: Short open reading frame-encoded peptides (SEPs), ranging from 2 to 100 amino acids, play important roles in various biological processes. In this study, we analyzed SEPs in five different brain regions of mice using mass spectrometry-based proteomics. We identified 373 SEPs, with approximately 83% of them being novel. Half of the identified SEPs were encoded by non-coding RNA, and about one-third showed orthology across species. Each brain region had specific SEPs, such as IP_1018875 in the frontal cortex, which may be related to autophagy and neuronal signaling. These findings expand our understanding of the mouse brain proteome and provide valuable insights for future studies on the function of SEPs.
Article
Clinical Neurology
Lu Sun, Rikst-Nynke Verkaik-Schakel, Knut Biber, Torsten Ploesch, Tsvetan Serchov
Summary: The research demonstrated that stress-induced depression-like behavior and antidepressant treatments are associated with epigenetic alterations of the Homer1 promoter, providing new insights into the mechanism of antidepressant treatment.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Article
Geriatrics & Gerontology
Francesco Bellanti, Vidyasagar Naik Bukke, Archana Moola, Rosanna Villani, Caterina Scuderi, Luca Steardo, Gianmauro Palombelli, Rossella Canese, Sarah Beggiato, Mario Altamura, Gianluigi Vendemiale, Gaetano Serviddio, Tommaso Cassano
Summary: This study investigated the therapeutic potential of ultramicronized palmitoylethanolamide (um-PEA) in 3 x Tg-AD mice. The results showed that um-PEA can improve the complex-I respiration rate and ATPase activity, as well as ATP content in the cortical mitochondria of the mice. However, um-PEA treatment did not improve the mitochondrial bioenergetics impairments and glutamate release in the hippocampus.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Lucia Caffino, Francesca Mottarlini, Sabrine Bilel, Giorgia Targa, Micaela Tirri, Coralie Maggi, Matteo Marti, Fabio Fumagalli
Summary: The study reveals that the expression of neuroplastic markers in the brain can be altered by low doses of MDPV or alpha-PVP, suggesting the widespread impact of these cathinones on brain plasticity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Marc Kermorgant, Jennifer Ben Salem, Jason S. Iacovoni, Denis Calise, Lionel Dahan, Bruno P. Guiard, Sebastien Lopez, Olivier Lairez, Antoine Lasbories, Nathalie Nasr, Anne Pavy Le-Traon, Francis Beaudry, Jean-Michel Senard, Dina N. Arvanitis
Summary: Desensitization of cardiac afferents relieves symptoms of anxiety and depression in mice. Proteomic analysis of frontal cortices suggests that the brain responds differently to stress originating from the heart, with a potential for unique signaling patterns under combined treatments. Dysregulation in circadian entrainment is observed across all treatment groups, indicating potential interference mechanisms in the combined treatment approach.
Review
Genetics & Heredity
Subramaniam Jayanthi, Michael T. McCoy, Jean Lud Cadet
Summary: Methamphetamine-use disorder is a serious condition that can lead to long-term changes in the brain and gene expression, highlighting the importance of researching the underlying mechanisms.
Article
Multidisciplinary Sciences
Harry MacKay, Chathura J. Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A. Waterland
Summary: Recent studies have confirmed that obesity is primarily a neurodevelopmental disease influenced by nutrition during critical ontogenic windows. This study examines the role of epigenetic mechanisms in establishing and maintaining the brain's energy balance circuitry, specifically in the hypothalamic arcuate nucleus. The results indicate that postnatal epigenetic maturation is cell type and sex specific, occurring in genomic regions associated with body mass index heritability. These findings provide valuable insights into the limited ontogenic windows for developmental programming of obesity and the sex differences in sensitivity, and offer a resource for epigenetic analysis of energy balance programming.
Article
Pharmacology & Pharmacy
Erbo Dong, Valentina Locci, Eleonora Gatta, Dennis R. Grayson, Alessandro Guidotti
MOLECULAR PHARMACOLOGY
(2019)
Meeting Abstract
Psychology, Developmental
David P. Gavin, Gian Paolo Vallerini, Shumila Kazmi, Marina Guizzetti, Maheen Kazmi
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
(2019)
Article
Neurosciences
Amul J. Sakharkar, Evan J. Kyzar, David P. Gavin, Huaibo Zhang, Ying Chen, Harish R. Krishnan, Dennis R. Grayson, Subhash C. Pandey
Article
Biochemistry & Molecular Biology
Harish R. Krishnan, Huaibo Zhang, Ying Chen, John Peyton Bohnsack, Annie W. Shieh, Handojo Kusumo, Jenny Drnevich, Chunyu Liu, Dennis R. Grayson, Mark Maienschein-Cline, Subhash C. Pandey
Summary: Using an animal model, this study used ATAC-seq and RNA-seq technologies to uncover the epigenomic and transcriptomic changes in the amygdala following acute ethanol exposure. The results suggest that these changes, particularly in the candidate gene Hif3a, are associated with anxiolytic effects and may contribute to the development of alcohol use disorder.
MOLECULAR PSYCHIATRY
(2022)
Article
Psychiatry
Hooriyah S. S. Rizavi, Omar S. S. Khan, Hui Zhang, Runa Bhaumik, Dennis R. R. Grayson, Ghanshyam N. N. Pandey
Summary: A dysregulated HPA axis is closely related to psychiatric disorders and suicide, but the mechanisms behind this dysregulation are not fully understood. Decreased expression of the glucocorticoid receptor (GR) gene, which can be influenced by epigenetic changes, is a strong indicator of impaired HPA axis control. This study focuses on analyzing the GR gene's 5'UTR in teenage suicide-completers to determine expression levels and epigenetic modifications, as well as examining the expression and epigenetic state of the FK506-binding protein 51 (FKBP5). The findings suggest that epigenetic regulation of the GR gene may contribute to long-lasting modifications in an individual's HPA axis response to stress.
TRANSLATIONAL PSYCHIATRY
(2023)
Meeting Abstract
Substance Abuse
H. R. Krishnan, Y. Chen, H. Zhang, A. W. Lasek, M. S. Brodie, M. Maienschein-Cline, D. R. Grayson, S. C. Pandey
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Meeting Abstract
Substance Abuse
L. Martins de Carvalho, H. Chen, H. Zhang, H. Krishnan, M. Maienschein-Cline, D. R. Grayson, S. C. Pandey, A. W. Lasek
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Meeting Abstract
Substance Abuse
E. Gatta, V. Saudagar, J. Auta, Y. Chen, D. R. Grayson, M. Maienschein-Cline, S. C. Pandey, A. Guidotti
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Meeting Abstract
Substance Abuse
S. C. Pandey, J. P. Bohnsack, H. R. Krishnan, Y. Chen, D. R. Grayson, H. Zhang
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2021)
Article
Neurosciences
Gian Paolo Vallerini, You-Hong Cheng, Kayla A. Chase, Rajiv P. Sharma, Handojo Kusumo, Shivani Khakhkhar, Douglas L. Feinstein, Marina Guizzetti, David P. Gavin
Meeting Abstract
Substance Abuse
D. R. Grayson, Y. Chen, H. R. Krishnan, H. Zhang, S. C. Pandey
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2020)
Meeting Abstract
Substance Abuse
G. P. Vallerini, K. A. Chase, S. Kazmi, M. Kazmi, D. L. Feinstein, D. P. Gavin
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2019)
Meeting Abstract
Substance Abuse
M. Kazmi, S. Kazmi, K. A. Chase, G. P. Vallerini, M. Guizzetti, D. P. Gavin
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2019)
Meeting Abstract
Substance Abuse
S. Kazmi, I. El-Khateeb, K. A. Chase, G. P. Vallerini, M. Kazmi, M. Guizzetti, D. P. Gavin
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2019)
Meeting Abstract
Substance Abuse
H. R. Krishnan, A. W. Shieh, H. Zhang, Y. Chen, C. Liu, D. R. Grayson, S. C. Pandey
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2019)