Botanical Medicines With Activity Against Stationary Phase Bartonella henselae by Xiao Ma, Jacob Leone, Sunjya Schweig, Ying Zhang, Stijn van der Veen

“…Among them, C. sanguinolenta, J. nigra, and P. cuspidatum could eradicate all stationary phase B. henselae cells within 7 days at 0.83 mg/mL or 1.25 mg/mL in drug exposure time-kill assays, whereas S. baicalensis and S. barbata showed relatively poor activity. These top hits were active against both stationary phase non-growing B. henselae and log phase growing B. henselae in minimum inhibitory concentration testing. …”
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Common genetic variation near MC4R has a sex-specific impact on human brain structure and eating behavior. by Annette Horstmann, Peter Kovacs, Stefan Kabisch, Yvonne Boettcher, Haiko Schloegl, Anke Tönjes, Michael Stumvoll, Burkhard Pleger, Arno Villringer

“…Recent genome-wide association studies (GWAS) identified obesity- and type 2 diabetes-associated genetic variants located within or near genes that modulate brain activity and development. Among the top hits is rs17782313 near MC4R, encoding for the melanocortin-4-receptor, which is expressed in brain regions that regulate eating. …”
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Inhibition of DNA glycosylases via small molecule purine analogs. by Aaron C Jacobs, Marcus J Calkins, Ajit Jadhav, Dorjbal Dorjsuren, David Maloney, Anton Simeonov, Pawel Jaruga, Miral Dizdaroglu, Amanda K McCullough, R Stephen Lloyd

“…This assay was miniaturized to a 1536-well format and used to screen small molecule libraries for inhibitors of the combined glycosylase/AP lyase activities. Among the top hits of these screens were several purine analogs, whose postulated presence in the active site of NEIL1 was consistent with the paradigm of NEIL1 recognition and excision of damaged purines. …”
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3D-QSAR studies on Maslinic acid analogs for Anticancer activity against Breast Cancer cell line MCF-7 by Sarfaraz Alam, Feroz Khan

“…After screening through Lipinski’s rule of five filter for oral bioavailability, ADMET risk filter for drug like features, and synthetic accessibility for chemical synthesis, out of 593 hits, 39 were left top hits. Docking screening was performed through identified potential targets namely, AKR1B10, NR3C1, PTGS2, and HER2. …”
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Genome-wide RNAi screen in IFN-γ-treated human macrophages identifies genes mediating resistance to the intracellular pathogen Francisella tularensis. by Hongwei Zhou, Glen DeLoid, Erica Browning, David J Gregory, Fengxiao Tan, Alice S Bedugnis, Amy Imrich, Henry Koziel, Igor Kramnik, Quan Lu, Lester Kobzik

“…These were prioritized according to mRNA expression in IFN-γ-primed and F. tularensis-challenged macrophages. A panel of 20 top hits was further assessed by re-testing using individual shRNAs or siRNAs in THP-1 cells, HMDMs and primary human lung macrophages. …”
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De Novo Transcriptome Analysis for Kentucky Bluegrass Dwarf Mutants Induced by Space Mutation. by Lu Gan, Rong Di, Yuehui Chao, Liebao Han, Xingwu Chen, Chao Wu, Shuxia Yin

“…In this study, two dwarf mutant selections of Kentucky bluegrass (A12 and A16) induced by space mutation were analyzed for the differentially expressed genes compared with the wild type (WT) by the high-throughput RNA-Seq technology. 253,909 unigenes were obtained by de novo assembly. 24.20% of the unigenes had a significant level of amino acid sequence identity to Brachypodium distachyon proteins, followed by Hordeum vulgare with 18.72% among the non-redundant (NR) Blastx top hits. Assembled unigenes were associated with 32 pathways using KEGG orthology terms and their respective KEGG maps. …”
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PRMT5 inhibition shows in vitro efficacy against H3K27M-altered diffuse midline glioma, but does not extend survival in vivo by Brown, EJ, Balaguer-Lluna, L, Cribbs, AP, Philpott, M, Campo, L, Browne, M, Wong, JF, Oppermann, U, Carcaboso, AM, Bullock, AN, Farnie, G

“…Here, we performed wider screening of an epigenetic inhibitor library and identified inhibitors of protein arginine methyltransferases (PRMTs) among the top hits reducing DMG cell viability. Two of the most effective inhibitors, LLY-283 and GSK591, were targeted against PRMT5 using distinct binding mechanisms and reduced the viability of a subset of DMG cells expressing wild-type TP53 and mutant ACVR1. …”

Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition by Shah Faisal, Syed Lal Badshah, Bibi Kubra, Mohamed Sharaf, Abdul-Hamid Emwas, Mariusz Jaremko, Mohnad Abdalla

“…More than one hundred different flavonoids were docked with the SARS-CoV-2 RdRp allosteric site through computational screening. The three top hits were Naringoside, Myricetin and Aureusidin 4,6-diglucoside. …”
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Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity by Maria Keller, Lydia Hopp, Xuanshi Liu, Tobias Wohland, Kerstin Rohde, Raffaella Cancello, Matthias Klös, Karl Bacos, Matthias Kern, Fabian Eichelmann, Arne Dietrich, Michael R. Schön, Daniel Gärtner, Tobias Lohmann, Miriam Dreßler, Michael Stumvoll, Peter Kovacs, Anna-Maria DiBlasio, Charlotte Ling, Hans Binder, Matthias Blüher, Yvonne Böttcher

“…The effects were further supported in additional independent cohorts. Our top hits might play a role in adipogenesis and differentiation, obesity, lipid metabolism, and adipose tissue expandability. …”
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Probing New Antileukemia Agents That Target FLT3 and BCL-2 from Traditional Concoctions through a Combination of Mass Spectrometry Analysis and Consensus Docking Methods by Adebayo A. Adeniyi, Joy Nkechinyere Adeniyi, Manimbulu Nlooto, Parvesh Singh

“…Venetoclax and gilteritinib, that target FLT3 and BCL-2 were ranked among the top hits, indicating the efficiency of this protocol without missing any potential drug. …”
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Proteasome Inhibitors Block DNA Repair and Radiosensitize Non-Small Cell Lung Cancer by Cron, Kyle R., Zhu, Kaya, Kushwaha, Deepa S., Hsieh, Grace, Merzon, Dmitry, Rameseder, Jonathan, Chen, Clark C., D'Andrea, Alan D., Kozono, David

“…These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. …”
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Targeting the Proteasome in Advanced Renal Cell Carcinoma: Complexity and Limitations of Patient-Individualized Preclinical Drug Discovery by Jielin Li, Laura Pohl, Julia Schüler, Nina Korzeniewski, Philipp Reimold, Adam Kaczorowski, Weibin Hou, Stefanie Zschäbitz, Cathleen Nientiedt, Dirk Jäger, Markus Hohenfellner, Anette Duensing, Stefan Duensing

“…Results: The proteasome inhibitor carfilzomib was among the top hits identified in three of four patients in which an in vitro drug screening could be performed successfully. …”
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Mechanism of Action and Structure–Activity Relationships of Tetracyclic Small Molecules Acting as Universal Positive Allosteric Modulators of the Cholecystokinin Receptor by Daniela G. Dengler, Kaleeckal G. Harikumar, Alice Yen, Eduard A. Sergienko, Laurence J. Miller

“…Extensive characterization of the two top “hits” from the previous effort demonstrated them to fulfill the desired pharmacologic profile. …”
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Novel Blood Biomarkers for a Diagnostic Workup of Acute Aortic Dissection by Anja Forrer, Felix Schoenrath, Michael Torzewski, Jens Schmid, Urlich F. W. Franke, Nora Göbel, Drahomir Aujesky, Christian M. Matter, Thomas F. Lüscher, Francois Mach, David Nanchen, Nicolas Rodondi, Volkmar Falk, Arnold von Eckardstein, Joanna Gawinecka

“…Subsequently, we validated top hits using conventional immunoassays and examined their expression in the aortic tissue. …”
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The TIP60-ATM axis regulates replication fork stability in BRCA-deficient cells by Emily M. Schleicher, Ashna Dhoonmoon, Lindsey M. Jackson, Jude B. Khatib, Claudia M. Nicolae, George-Lucian Moldovan

“…Moreover, we performed a series of genome-wide CRISPR knockout genetic screens to identify genetic determinants of the cellular sensitivity to ATM inhibition in wildtype and BRCA2-knockout cells, and validated the top hits from multiple screens. We provide a valuable list of common genes which regulate the response to multiple ATM inhibitors. …”
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Genome-wide association study of periodontal pocketing in Finnish adults by Paula Tegelberg, Jussi Miikkael Leppilahti, Atte Ylöstalo, Tellervo Tervonen, Johannes Kettunen, Anna Liisa Suominen, Pekka Ylöstalo

“…Results Genome-wide significant associations with the number of teeth with ≥ 4 mm deep pockets were not found at the p-level of < 5 × 10−8, while in total 17 loci reached the p-level of 5 × 10−6. Of the top hits, SNP rs4444613 in chromosome 20 showed the strongest association (p = 1.35 × 10−7). …”
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Genome-wide CRISPR screen reveals PSMA6 to be an essential gene in pancreatic cancer cells by Jesse Bakke, William C. Wright, Anthony E. Zamora, Peter Oladimeji, Jeremy Chase Crawford, Christopher T. Brewer, Robert J. Autry, William E. Evans, Paul G. Thomas, Taosheng Chen

“…Methods We used a negative-selection genome-wide CRISPR screen to identify essential genes in the PANC-1 human pancreatic carcinoma cell line. We validated the top hits with follow-up siRNA screens, using the HPNE, HPAF-II, AsPC-1, and Mia PaCa-2 cell lines. …”
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In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA2AR antagonists for the treatment of Parkinson's disease by Boulaamane Yassir, Ibrahim Mahmoud A. A., Britel Mohammed Reda, Maurady Amal

“…Our findings revealed two natural products among the top hits: CNP0202316 and CNP0365210 fulfill the requirements of drugs acting on the brain. …”
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Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal Pathogen <i>Histoplasma capsula... by Charlotte Berkes, Jimmy Franco, Maxx Lawson, Katelynn Brann, Jessica Mermelstein, Daniel Laverty, Allison Connors

“…Our approach identified seven compounds with an elongated hydrophobic polyaromatic structure, five of which share a molecular motif including a urea unit linking a halogenated benzene ring and a <i>para</i>-substituted polyaromatic group. The top hits include the cancer therapeutic Sorafenib, which inhibits growth of <i>Histoplasma</i> in vitro and in a macrophage infection model with low host cell cytotoxicity. …”
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Exploring the Potency of <i>Nigella sativa</i> Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations by Ari Hardianto, Muhammad Yusuf, Ika Wiani Hidayat, Safri Ishmayana, Ukun Mochammad Syukur Soedjanaatmadja

“…Subsequently, virtual screening campaigns using a molecular docking method were performed, with N3 inhibitor and leupeptin as reference ligands. The top hits were analyzed further using a molecular dynamics simulation approach. …”
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