keyword
https://read.qxmd.com/read/38505842/discovery-and-characterization-of-active-cbp-ep300-degraders-targeting-the-hat-domain
#21
JOURNAL ARTICLE
Iván Cheng-Sánchez, Katherine A Gosselé, Leonardo Palaferri, Mariia S Kirillova, Cristina Nevado
Proteolysis Targeting Chimeras (PROTACs) are bifunctional molecules that simultaneously bind an E3 ligase and a protein of interest, inducing degradation of the latter via the ubiquitin-proteasome system. Here we present the development of degraders targeting CREB-binding protein (CBP) and E1A-associated protein (EP300)-two homologous multidomain enzymes crucial for enhancer-mediated transcription. Our PROTAC campaign focused on CPI-1612, a reported inhibitor of the histone acetyltransferase (HAT) domain of these two proteins...
March 14, 2024: ACS Medicinal Chemistry Letters
https://read.qxmd.com/read/38505100/a-toolbox-for-decoding-bci-commands-based-on-event-related-potentials
#22
JOURNAL ARTICLE
Christoph Reichert, Catherine M Sweeney-Reed, Hermann Hinrichs, Stefan Dürschmid
Commands in brain-computer interface (BCI) applications often rely on the decoding of event-related potentials (ERP). For instance, the P300 potential is frequently used as a marker of attention to an oddball event. Error-related potentials and the N2pc signal are further examples of ERPs used for BCI control. One challenge in decoding brain activity from the electroencephalogram (EEG) is the selection of the most suitable channels and appropriate features for a particular classification approach. Here we introduce a toolbox that enables ERP-based decoding using the full set of channels, while automatically extracting informative components from relevant channels...
2024: Frontiers in Human Neuroscience
https://read.qxmd.com/read/38500836/the-winged-helix-domain-of-morf-binds-cpg-islands-and-the-taz2-domain-of-p300
#23
JOURNAL ARTICLE
Dustin C Becht, Akinori Kanai, Soumi Biswas, Mohamed Halawa, Lei Zeng, Khan L Cox, Michael G Poirier, Ming-Ming Zhou, Xiaobing Shi, Akihiko Yokoyama, Tatiana G Kutateladze
Acetylation of histones by lysine acetyltransferases (KATs) provides a fundamental mechanism by which chromatin structure and transcriptional programs are regulated. Here, we describe a dual binding activity of the first winged helix domain of human MORF KAT (MORFWH1 ) that recognizes the TAZ2 domain of p300 KAT (p300TAZ2 ) and CpG rich DNA sequences. Structural and biochemical studies identified distinct DNA and p300TAZ2 binding sites, allowing MORFWH1 to independently engage either ligand. Genomic data show that MORF/MOZWH1 colocalizes with H3K18ac, a product of enzymatic activity of p300, on CpG rich promoters of target genes...
April 19, 2024: IScience
https://read.qxmd.com/read/38493498/yy1-lactylation-aggravates-autoimmune-uveitis-by-enhancing-microglial-functions-via-inflammatory-genes
#24
JOURNAL ARTICLE
Jiaxing Huang, Xiaotang Wang, Na Li, Wei Fan, Xingran Li, Qian Zhou, Jiangyi Liu, Wanqian Li, Zhi Zhang, Xiaoyan Liu, Shuhao Zeng, Hui Yang, Meng Tian, Peizeng Yang, Shengping Hou
Activated microglia in the retina are essential for the development of autoimmune uveitis. Yin-Yang 1 (YY1) is an important transcription factor that participates in multiple inflammatory and immune-mediated diseases. Here, an increased YY1 lactylation in retinal microglia within in the experimental autoimmune uveitis (EAU) group is observed. YY1 lactylation contributed to boosting microglial activation and promoting their proliferation and migration abilities. Inhibition of lactylation suppressed microglial activation and attenuated inflammation in EAU...
March 17, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38493361/p300-parameters-in-major-depressive-disorder-a-systematic-review-and-meta-analysis
#25
REVIEW
Mehmet Kemal Arıkan, Reyhan İlhan, Özden Orhan, Muhammed Taha Esmeray, Şenol Turan, Şakir Gica, Hasan Bakay, Oliver Pogarell, Kâşif Nevzat Tarhan, Barış Metin
OBJECTIVES: Event-related potential measures have been extensively studied in mental disorders. Among them, P300 amplitude and latency reflect impaired cognitive abilities in major depressive disorder (MDD). The present systematic review and meta-analysis was conducted to investigate whether patients with MDD differ from healthy controls (HCs) with respect to P300 amplitude and latency. METHODS: PubMed and Web of Science databases were searched from inception to 15 January 2023 for case-control studies comparing P300 amplitude and latency in patients with MDD and HCs...
March 17, 2024: World Journal of Biological Psychiatry
https://read.qxmd.com/read/38493218/hoxd3-promotes-the-migration-and-angiogenesis-of-hepatocellular-carcinoma-via-modifying-hepatocellular-carcinoma-cells-exosome-delivered-ccr6-and-regulating-chromatin-conformation-of-ccl20
#26
JOURNAL ARTICLE
Lumin Wang, Chenyang Qiao, Lili Han, Xiaofei Wang, Jiyu Miao, Li Cao, Chen Huang, Jinhai Wang
Angiogenesis plays an essential role in the microenvironment of hepatocellular carcinoma (HCC). HOXD3 is involved in the metastasis and invasion of HCC cells; Whereas the underlying molecular mechanisms in the microenvironment of HCC remain unknown. Wound healing, transwell invasion, tube formation and spheroid sprouting assays were carried out to identify the effects of HCC-HOXD3-exosomes and genes on the migration of HCC cells. ChIP-PCR was applied to test the binding region of HOXD3 on CCR6, Med15, and CREBBP promoter...
March 16, 2024: Cell Death & Disease
https://read.qxmd.com/read/38491114/plasma-extracellular-vesicle-micrornas-reflecting-the-therapeutic-effect-of-the-cbp-%C3%AE-catenin-inhibitor-pri-724-in-patients-with-liver-cirrhosis
#27
JOURNAL ARTICLE
Mayu Yoshida, Juntaro Matsuzaki, Koji Fujita, Masamichi Kimura, Tomohiro Umezu, Noi Tokuda, Tomoko Yamaguchi, Masahiko Kuroda, Takahiro Ochiya, Yoshimasa Saito, Kiminori Kimura
There is an unmet need for antifibrotic therapies to prevent the progression of liver cirrhosis. Previously, we conducted an exploratory trial to assess the safety and antifibrotic efficacy of PRI-724, a selective CBP/β-catenin inhibitor, in patients with liver cirrhosis. PRI-724 was well tolerated and exerted a potential antifibrotic effect. Here, we investigated whether the profiles of circulating microRNAs packaged in extracellular vesicles (EV-miRNAs) are associated with responses to liver fibrosis treatments...
March 15, 2024: Scientific Reports
https://read.qxmd.com/read/38490636/parageobacillus-thermoglucosidasius-as-an-emerging-thermophilic-cell-factory
#28
REVIEW
Miguel Paredes-Barrada, Panagiotis Kopsiaftis, Nico J Claassens, Richard van Kranenburg
Parageobacillus thermoglucosidasius is a thermophilic and facultatively anaerobic microbe, which is emerging as one of the most promising thermophilic model organisms for metabolic engineering. The use of thermophilic microorganisms for industrial bioprocesses provides the advantages of increased reaction rates and reduced cooling costs for bioreactors compared to their mesophilic counterparts. Moreover, it enables starch or lignocellulose degradation and fermentation to occur at the same temperature in a Simultaneous Saccharification and Fermentation (SSF) or Consolidated Bioprocessing (CBP) approach...
March 13, 2024: Metabolic Engineering
https://read.qxmd.com/read/38490340/epigenetics-of-diabetes-a-bioinformatic-approach
#29
REVIEW
Sulistyo Emantoko Dwi Putra, Farizky Martriano Humardani, Yulanda Antonius, Jonathan Jonathan, Lisa Thalia Mulyanata
The adaptability of epigenetics offers a compelling research avenue, notably in the context of Type 2 Diabetes Mellitus (T2DM) biomarkers and provides a nuanced approach to managing biological systems for diagnosis. However, challenges such as DNA degradation during methylation studies are prominent, especially with cell-free DNA (cfDNA) which is present in small quantities in plasma, calling for innovative solutions. To tackle these challenges, four methodological approaches have been identified: firstly, selecting an appropriate DNA extraction method and enhancing DNA yield through amplification; secondly, adapting bisulfite modification techniques to minimize DNA degradation; thirdly, utilizing tools capable of working with minimal DNA quantities; and lastly, employing bisulfite-free methylation techniques...
March 13, 2024: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://read.qxmd.com/read/38490327/epic-0628-abrogates-hotair-ezh2-interaction-and-enhances-the-temozolomide-efficacy-via-promoting-atf3-expression-and-inhibiting-dna-damage-repair-in-glioblastoma
#30
JOURNAL ARTICLE
Eryan Yang, Biao Hong, Yunfei Wang, Qixue Wang, Jixing Zhao, Xiaoteng Cui, Ye Wu, Shixue Yang, Dongyuan Su, Xiaomin Liu, Chunsheng Kang
The efficacy of temozolomide (TMZ) treatment in glioblastoma (GBM) is influenced by various mechanisms, mainly including the level of O6 -methylguanine-DNA methyltransferase (MGMT) and the activity of DNA damage repair (DDR) pathways. In our previous study, we had proved that long non-coding RNA HOTAIR regulated the GBM progression and mediated DDR by interacting with EZH2, the catalytic subunit of PRC2. In this study, we developed a small-molecule inhibitor called EPIC-0628 that selectively disrupted the HOTAIR-EZH2 interaction and promoted ATF3 expression...
March 13, 2024: Cancer Letters
https://read.qxmd.com/read/38490050/role-of-transcriptional-cofactors-in-cardiovascular-diseases
#31
REVIEW
Shuqing Mao, Chao Song, Hong Huang, Yali Nie, Kai Ding, Jian Cui, Jinwei Tian, Huifang Tang
Cardiovascular disease is a main cause of mortality in the world and the highest incidence of all diseases. However, the mechanism of the pathogenesis of cardiovascular disease is still unclear, and we need to continue to explore its mechanism of action. The occurrence and development of cardiovascular disease is significantly associated with genetic abnormalities, and gene expression is affected by transcriptional regulation. In this complex process, the protein-protein interaction promotes the RNA polymerase II to the initiation site...
March 11, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38486318/free-cognitive-capacity-assessed-by-the-p300-method-during-manual-docking-training-in-space
#32
JOURNAL ARTICLE
Juri Akardevic Bubeev, Bernd Johannes, Tatyana I Kotrovska, Darya Schastlivtseva, Sergey Bronnikov, Hans-Juergen Hoermann, Anthony W K Gaillard
INTRODUCTION: The classical P300 brain potential method was used to assess the cognitive capacity during training of manual docking in space. The aim of the study was to enhance the safety of this operation during a mission. METHODS: To examine this, N = 8 cosmonauts had to perform the manually controlled docking task simultaneously with an acoustic monitoring task. The P300 component was evoked by the acoustic stimuli of the secondary task. The docking task had to be executed at three difficulty levels: low (station not turning); medium (station turning around one axis); and difficult (station turning around three axes)...
April 1, 2024: Aerospace Medicine and Human Performance
https://read.qxmd.com/read/38482749/aspirin-mediated-acetylation-of-sirt1-maintains-intestinal-immune-homeostasis
#33
JOURNAL ARTICLE
Liangguo Xie, Chaoqun Li, Chao Wang, Zhen Wu, Changchun Wang, Chunyu Chen, Xiaojian Chen, Dejian Zhou, Qiang Zhou, Ping Lu, Chen Ding, Chen-Ying Liu, Jinzhong Lin, Xumin Zhang, Xiaofei Yu, Wei Yu
Aspirin, also named acetylsalicylate, can directly acetylate the side-chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic-labeling aspirin-d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+ -dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity...
March 14, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38482308/effect-of-pranayama-on-sympatho-vagal-imbalance-and-cognitive-deficit-in-premenstrual-syndrome
#34
JOURNAL ARTICLE
A Jothi Marie Feula, Dhanalakshmi Yerrabelli, Gopal Krushna Pal
CONTEXT: Premenstrual syndrome (PMS) is a prevalent and often neglected condition that affects around 80% of women of reproductive age. In PMS, abnormal fluctuations in gonadal hormones cause altered homeostasis, resulting in sympatho-vagal imbalance and poor cognition. AIM: To compare autonomic function parameters and cognitive performance between PMS and control groups, and to study the effect of pranayama on the above parameters in PMS women. SETTINGS AND DESIGN: It was a randomized control trial...
January 2024: Journal of Family Medicine and Primary Care
https://read.qxmd.com/read/38482024/synapse-related-serum-and-p300-biomarkers-predict-the-occurrence-of-mild-cognitive-impairment-in-depression
#35
JOURNAL ARTICLE
Zongwei Xue, Xiaoyan Zhu, Wenqi Wu, Yan Zhu, Yuhao Xu, Ming Yu
BACKGROUND: Cognitive impairment is one of the common concomitant symptoms of depression. The aims of the present study were to predict the occurrence of mild cognitive impairment (MCI) in patients with depression. METHODS: In this study, 217 patients with depression were recruited. Demographic data, serum indices and ERP indices from all participants were collected in the baseline period. The participants were followed for one year, and data from 200 patients were included in final analysis...
2024: Neuropsychiatric Disease and Treatment
https://read.qxmd.com/read/38480884/evolutionary-trajectories-of-small-cell-lung-cancer-under-therapy
#36
JOURNAL ARTICLE
Julie George, Lukas Maas, Nima Abedpour, Maria Cartolano, Laura Kaiser, Rieke N Fischer, Andreas H Scheel, Jan-Philipp Weber, Martin Hellmich, Graziella Bosco, Caroline Volz, Christian Mueller, Ilona Dahmen, Felix John, Cleidson Padua Alves, Lisa Werr, Jens Peter Panse, Martin Kirschner, Walburga Engel-Riedel, Jessica Jürgens, Erich Stoelben, Michael Brockmann, Stefan Grau, Martin Sebastian, Jan A Stratmann, Jens Kern, Horst-Dieter Hummel, Balazs Hegedüs, Martin Schuler, Till Plönes, Clemens Aigner, Thomas Elter, Karin Toepelt, Yon-Dschun Ko, Sylke Kurz, Christian Grohé, Monika Serke, Katja Höpker, Lars Hagmeyer, Fabian Doerr, Khosro Hekmath, Judith Strapatsas, Karl-Otto Kambartel, Geothy Chakupurakal, Annette Busch, Franz-Georg Bauernfeind, Frank Griesinger, Anne Luers, Wiebke Dirks, Rainer Wiewrodt, Andrea Luecke, Ernst Rodermann, Andreas Diel, Volker Hagen, Kai Severin, Roland T Ullrich, Hans Christian Reinhardt, Alexander Quaas, Magdalena Bogus, Cornelius Courts, Peter Nürnberg, Kerstin Becker, Viktor Achter, Reinhard Büttner, Jürgen Wolf, Martin Peifer, Roman K Thomas
The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown1-3 . Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity...
March 13, 2024: Nature
https://read.qxmd.com/read/38479676/pesticide-induced-alterations-in-zebrafish-danio-rerio-behavior-histology-dna-damage-and-mrna-expression-an-integrated-approach
#37
JOURNAL ARTICLE
M Bianchi, E V Paravani, M G Acosta, L M Odetti, M F Simoniello, G L Poletta
To assess the impact of glyphosate and 2,4-D herbicides, as well as the insecticide imidacloprid, both individually and in combination, the gills of adult zebrafish were used due to their intimate interaction with chemicals diluted in water. Bioassays were performed exposing the animals to the different pesticides and their mixture for 96 h. The behavior of the fish was analyzed, a histological examination of the gills was carried out, and the genotoxic effects were also analyzed by means of the comet assay (CA) and the change in the expression profiles of genes involved in the pathways of the oxidative stress and cellular apoptosis...
March 11, 2024: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://read.qxmd.com/read/38477974/discovery-of-cbpd-268-as-an-exceptionally-potent-and-orally-efficacious-cbp-p300-protac-degrader-capable-of-achieving-tumor-regression
#38
JOURNAL ARTICLE
Zhixiang Chen, Mi Wang, Dimin Wu, Longchuan Bai, Tianfeng Xu, Hoda Metwally, Yu Wang, Donna McEachern, Lijie Zhao, Ruiting Li, John Takyi-Williams, Meilin Wang, Lu Wang, Qiuxia Li, Bo Wen, Duxin Sun, Shaomeng Wang
CBP/p300 proteins are key epigenetic regulators and promising targets for the treatment of castration-resistant prostate cancer and other types of human cancers. Herein, we report the discovery and characterization of CBPD-268 as an exceptionally potent, effective, and orally efficacious PROTAC degrader of CBP/p300 proteins. CBPD-268 induces CBP/p300 degradation in three androgen receptor-positive prostate cancer cell lines, with DC50 ≤ 0.03 nM and D max > 95%, leading to potent cell growth inhibition...
March 13, 2024: Journal of Medicinal Chemistry
https://read.qxmd.com/read/38474792/effects-of-dietary-colostrum-basic-protein-on-bone-growth-and-calcium-absorption-in-mice
#39
JOURNAL ARTICLE
Yiran Zhang, Ziyu Qiao, Jiale Yu, Chenhong Shi, Rui Quan, Wen Zhang, Ran Bi, Hongliang Li, Wentao Qian, Menghui Wang, Yixuan Li
Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae...
February 27, 2024: Nutrients
https://read.qxmd.com/read/38473705/pathogenic-variants-associated-with-epigenetic-control-and-the-notch-pathway-are-frequent-in-classic-hodgkin-lymphoma
#40
JOURNAL ARTICLE
Antonio Santisteban-Espejo, Irene Bernal-Florindo, Pedro Montero-Pavon, Jose Perez-Requena, Lidia Atienza-Cuevas, Maria Del Carmen Fernandez-Valle, Ana Villalba-Fernandez, Marcial Garcia-Rojo
Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80-90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients...
February 20, 2024: International Journal of Molecular Sciences
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