dyphAI dynamic pharmacophore modeling with AI: a tool for efficient screening of new acetylcholinesterase inhibitors by Yasser Hayek-Orduz, Dorian Armando Acevedo-Castro, Dorian Armando Acevedo-Castro, Juan Sebastián Saldarriaga Escobar, Brandon Eli Ortiz-Domínguez, María Francisca Villegas-Torres, Paola A. Caicedo, Álvaro Barrera-Ocampo, Natalie Cortes, Edison H. Osorio, Andrés Fernando González Barrios

“…In contrast, molecule 3 (P-617769798) showed a higher IC50 value, and molecules 1 (P-14421887) and 2 (P-25746649) yielded inconsistent results, likely due to solubility issues in the experimental setup. …”
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L-glutaminase synthesis by Klebsiella pneumoniae (AS KP 23) isolated from clinical strain, and its efficacy against human hepatocellular and breast cancer cell lines by Lina J. Abdel-Hafez, Eman Y. T. Elariny, Asmaa E. Ibrahim, Mahmoud E. F. Abdel-Haliem

“…L-glutaminase has been cited as the most potent molecule that inhibits the proliferation of cancer cells, which significantly raises the possible applicability of cancer therapy and the possibility of its application as an alternative drug to chemotherapy. …”
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Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via redu... by Xu Miao, Shi Run, Yang Jie, Chen Heng, Liu Shihua, Yu Shupei, Li Sasa, He Wenqiang, Sy Man-Sun, Lu Mingjian, Zhang Huixia, Li Chaoyang

“…Therefore, there may be molecule(s) that can negate the deleterious effects of overexpressing C-P4HAs during cancer progression. …”
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Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells by Li-Xian Yang, Chuangye Qi, Si Lu, Xiang-Shi Ye, Parnaz Merikhian, Du-Yu Zhang, Tao Yao, Jiang-Sha Zhao, Ying Wu, Yongshi Jia, Bo Shan, Jinghai Chen, Xiaozhou Mou, Jia You, Wenbo Li, Yu-Xiong Feng

“…Importantly, a small molecule inhibitor targeting ATF4 translation effectively mitigates liver fibrosis. …”
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Lactate accumulation promotes immunosuppression and fibrotic transformation of bone marrow microenvironment in myelofibrosis by Mariarita Spampinato, Cesarina Giallongo, Sebastiano Giallongo, Enrico La Spina, Andrea Duminuco, Lucia Longhitano, Rosario Caltabiano, Lucia Salvatorelli, Giuseppe Broggi, Elisabetta P. Pricoco, Vittorio Del Fabro, Ilaria Dulcamare, Antonio Massimo DI Mauro, Alessandra Romano, Francesco Di Raimondo, Giovanni Li Volti, Giuseppe A. Palumbo, Daniele Tibullo

“…There is great evidence indicating that tumor microenvironment is characterized by high lactate levels, acting not only as an energetic source, but also as a signaling molecule. Methods To test the involvement of lactate in MF milieu transformation, we measured its levels in MF patients’ sera, eventually finding a massive accumulation of this metabolite, which we showed to promote the expansion of immunosuppressive subsets. …”
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Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species by Tatevik Sargsyan, Lala Stepanyan, Henrik Panosyan, Heghine Hakobyan, Monika Israyelyan, Avetis Tsaturyan, Nelli Hovhannisyan, Caterina Vicidomini, Anna Mkrtchyan, Ashot Saghyan, Giovanni N. Roviello

“…On the other hand, the protected amino acid <b>3a</b> demonstrated consistent inhibition across all tested <i>Aspergillus</i> strains, but with an IC₅₀ value of 267.86 µM for <i>Aspergillus flavus</i>, it was less potent than fluconazole (IC₅₀ 184.64 µM), still showing some potential as a good antifungal molecule. Overall, our findings indicate that the synthesized 1,2,4-triazolyl derivatives <b>3a</b> and <b>7a</b> hold significant promise as potential antifungal agents in treating <i>Aspergillus</i>-induced diseases in cattle, as well as for broader applications in human health. …”
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Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma by Marie Törngren, Rong Fan, Eline Menu, Helena Eriksson, Karin Vanderkerken, Andrew Chantry, Hatice Satilmis, Niels Vandewalle, Emma Verheye, Philip Vlummens, Anke Maes, Catharina Muylaert, Elke De Bruyne, Holly Evans, Nathan De Beule, Dirk Hose, Ken Maes, Karine Breckpot, Kim De Veirman

“…Tasquinimod, a small molecule inhibitor of S100A9, is currently in a phase Ib/IIa clinical trial in MM patients (NCT04405167). …”
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Impact of antibody architecture and paratope valency on effector functions of bispecific NKp30 x EGFR natural killer cell engagers by Ammelie Svea Boje, Lukas Pekar, Katharina Koep, Britta Lipinski, Brian Rabinovich, Andreas Evers, Carina Lynn Gehlert, Steffen Krohn, Yanping Xiao, Simon Krah, Rinat Zaynagetdinov, Lars Toleikis, Sven Poetzsch, Matthias Peipp, Stefan Zielonka, Katja Klausz

“…However, the fusion of sdAbs can have a slight impact on the NK cell release of immunomodulatory cytokines, as well as on the pharmacokinetic profile of the NKCE due to unfavorable spatial orientation within the molecule architecture. Ultimately, our findings reveal novel insights for the engineering of potent NKCEs triggering the NKp30 axis.…”
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Aerobic exercise alleviates statin-induced PCSK9 upregulation by increasing epoxyeicosatrienoic acid levels through the FoxO3a–Sirt6 axis by Jiahui Hu, Hao Lei, Jingyuan Chen, Leiling Liu, Yajun Gui, Kaijun Sun, Danyan Xu

“…Background: Statins are the cornerstone of low-density lipoprotein cholesterol (LDL-C)-lowering therapy; however, the therapeutic efficacy of statins in countering atherosclerotic cardiovascular disease (ASCVD) is compromised by the concurrent elevation of proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal molecule that increases LDL-C levels. Aerobic exercise lowers PCSK9 levels, but the underlying mechanism remains unclear. …”
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Frk positively regulates innate antiviral immunity by phosphorylating TBK1 by Xiaomei Zhang, Ying You, Tingrong Xiong, Tingrong Xiong, Xiaokai Zhang, Haibo Wang, Jinxia Geng, Miao Wang, Yanyan Xu, Shanshan Gao, Shanshan Gao, Xiaoyan Wu, Yue Zheng, Xianhua Wen, Haoyu Yang, Yu Wang, Yu Wang, Xiaohua Wen, Congcong Zhao

“…In this study, we validated the function of Fyn-related kinase (Frk) in the antiviral innate immune response and identified the direct target molecule of Frk in the IFN-β signaling pathway. Furthermore, we elucidated the mechanism by which Frk phosphorylates TBK1 during infection and the role of Frk in IFN-β production. …”
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LINC01089 governs the miR-1287-5p/HSPA4 axis to negatively regulate osteogenic differentiation of mesenchymal stem cells by Hao Zou, Fei Hu, Xin Wu, Bin Xu, Guifeng Shang, Dong An, Dehao Qin, Xiaolei Zhang, Aofei Yang

“…HSPA4 is a downstream function molecule of the LINC01089/miR-1287-5p pathway; miR-1287-5p negatively modulated HSPA4 levels and attenuated its functional effects. …”
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Anti-Inflammatory and Healing Activity of the Hydroalcoholic Fruit Extract of Solanum diploconos (Mart.) Bohs by Larissa Benvenutti, Roberta Nunes, Ivonilce Venturi, Silvia Aparecida Ramos, Milena Fronza Broering, Fernanda Capitanio Goldoni, Sarah Eskelsen Pavan, Maria Verônica Dávila Pastor, Angela Malheiros, Nara Lins Meira Quintão, Elizabeth Soares Fernandes, José Roberto Santin

“…In vitro fMLP-induced chemotaxis, LPS-induced inflammatory mediator levels (cytokines by ELISA and NO release by Griess reaction), and adhesion molecule expression (CD62L, CD49d, and CD18, by flow-cytometry) were assessed in neutrophils treated with different concentrations of the extract. …”
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Sensitive Detection of Lasalocid Residue in Chicken by Surface Enhanced Raman Spectroscopy by Yao WANG, Yingying SUN, Yubing JING, Xiyan YANG, Yanfei LI, Jiaxiang HUANG, Xiujin CHEN, Zhaozhou LI, Li CAO, Huaibin KANG

“…In this study, gold nanoparticles (AuNPs) with different particle sizes were first prepared, AuNPs with the optimal particle size were selected as the substrate according to SERS effect, and 4-aminophenthiophenol (PATP) was used as the probe molecule to evaluate the recurrence of AuNPs substrate. …”
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PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function by Laura C. Echeverri Tirado, Mohamed A. Ghonim, Jeffrey Wang, Amir A. Al-Khami, Dorota Wyczechowska, Hanh H. Luu, Hogyoung Kim, Maria Dulfary Sanchez-Pino, José Yélamos, Lina M. Yassin, A. Hamid Boulares

“…PARP-1 inhibition significantly reduced the migration of DCs to the lungs of ovalbumin-challenged mice, which was associated with a concomitant reduction in lung levels of the adhesion molecule VCAM-1. The requirement of PARP-1 for VCAM-1 expression was confirmed using endothelial and lung smooth muscle cells. …”
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GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth by Ana Alvarez de Cienfuegos, Lawrence H Cheung, Khalid A Mohamedali, Michael G Rosenblum, Brian Aguirre, Cheng-Hsiang Lu, Anubhav Chandla, Nidhi Kejriwal, Lucia Liu, Ann M Chan, SuYin Kok, Sergio Duarte, David Casero, Madhuri Wadehra

“…Background Granzyme B (GrB) is a key effector molecule, delivered by cytotoxic T lymphocytes and natural killer cells during immune surveillance to induce cell death. …”
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Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells by Gui-Qi Zhu, Zheng Tang, Tian-Hao Chu, Biao Wang, Shi-Ping Chen, Chen-Yang Tao, Jia-Liang Cai, Rui Yang, Wei-Feng Qu, Yi Wang, Qian-Fu Zhao, Run Huang, Meng-Xin Tian, Yuan Fang, Jun Gao, Xiao-Ling Wu, Jian Zhou, Wei-Ren Liu, Zhi Dai, Ying-Hong Shi, Jia Fan

“…The inactivation of SRSF1 in tumor cells reduces transcription factors, including c-Jun, c-myc, and JunB, facilitating glycolytic metabolism reprogramming, which restores CD8+ T cell function and inhibits tumor growth. The small-molecule inhibitor TN2008 targets SRSF1, boosting antitumor immune responses and improving immunotherapy effectiveness in mouse models. …”
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A novel high-throughput screen identifies phenazine-1-carboxylic acid as an inhibitor of African swine fever virus replication in primary porcine alveolar macrophages by Jing Lan, Rui Luo, Di Liu, Changxing Qi, Xin Song, Zhanhao Lu, Ruojia Huang, Yuying Yang, Yuan Sun, Yonghui Zhang, Tao Wang, Hua-Ji Qiu

“…Using the HTS platform established with rASFV-Gluc/EGFP, we screened and identified phenazine-1-carboxylic acid (PCA) as an effective inhibitor of ASFV replication from 246 small molecule compounds in PAMs. Importantly, PCA was found to reduce ASFV replication by as much as 100-fold at a concentration of 25 μM. …”
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Unraveling the impact of SARS-CoV-2 mutations on immunity: insights from innate immune recognition to antibody and T cell responses by Rafael Bayarri-Olmos, Rafael Bayarri-Olmos, Adrian Sutta, Adrian Sutta, Anne Rosbjerg, Anne Rosbjerg, Mie Mandal Mortensen, Charlotte Helgstrand, Per Franklin Nielsen, Laura Pérez-Alós, Beatriz González-García, Laust Bruun Johnsen, Finn Matthiesen, Thomas Egebjerg, Cecilie Bo Hansen, Alessandro Sette, Alessandro Sette, Alba Grifoni, Ricardo da Silva Antunes, Peter Garred, Peter Garred

“…The pattern recognition molecule mannose-binding lectin (MBL) has been shown to recognize the spike protein. …”
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FGF21 and APOA1 mRNA-based therapies for the treatment of experimental acute pancreatitis by Amaya Lopez-Pascual, Eva Santamaria, Nuria Ardaiz, Iker Uriarte, Tiffany Palmer, Anne-Renee Graham, Celia Gomar, Roberto C. Barbero, M. Ujue Latasa, Maria Arechederra, Jesus M. Urman, Carmen Berasain, Antonio Fontanellas, Carlos L. del Rio, Maite G. Fernandez-Barrena, Paolo G.V. Martini, Joshua R. Schultz, Pedro Berraondo, Matias A. Avila

“…While individual treatments effectively reduced pancreatic injury, the APOA1-FGF21 fusion molecule did not exhibit superior activity. Liver-targeted LNP-mRNA administration may offer a promising approach for treating AP, leveraging endogenous production pathways for therapeutic proteins. …”
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An exploratory study of INPP4B, a biomarker of gemcitabine chemoresistance in pancreatic cancer by REN Jiaqiang, WU Shuai, SU Tong, LI Jie, HAN Liang, WU Zheng

“…Co-expressed genes were screened using real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), Western blot and immunohistochemistry to verify the expression levels of target molecules. Surgical specimens from 70 patients diagnosed with pancreatic adenocarcinoma at the First Affiliated Hospital of Xi'an Jiao Tong University between June 2018 and June 2021 were analyzed. …”
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