Article
Chemistry, Physical
Haiyan Yang, Zheyuan Shen, Linxiang Luo, Jian Gao, Sikang Chen, Jinxin Che, Lei Xu, Meijuan Wu, Xiaowu Dong
Summary: CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2), members of the GPCRs family, play important roles in cancer cell proliferation, apoptosis, and angiogenesis. The high sequence homology between CXCR1 and CXCR2 poses a challenge in developing selective antagonists. Through computational methods, it was discovered that the differences in the amino acids ASN311 on CXCR1 and LYS320 on CXCR2 are the main reason for the different antagonistic abilities of CXCR1/2, providing important clues for the development of selective CXCR1/2 antagonists.
CHEMICAL PHYSICS LETTERS
(2022)
Article
Oncology
Paola Verachi, Francesca Gobbo, Fabrizio Martelli, Andrea Martinelli, Giuseppe Sarli, Andrew Dunbar, Ross L. Levine, Ronald Hoffman, Maria Teresa Massucci, Laura Brandolini, Cristina Giorgio, Marcello Allegretti, Anna Rita Migliaccio
Summary: This study demonstrates that Reparixin treatment can reduce fibrosis in a mouse model of myelofibrosis by decreasing the expression of TGF-beta 1 and collagen III while increasing the expression of GATA1. These findings provide a preclinical rationale for further evaluating the use of Reparixin in the treatment of patients with myelofibrosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Polymer Science
Tung Phuc Vo, Ming Hui Chua, Shi Jun Ang, Kang Le Osmund Chin, Xiang Yun Debbie Soo, Zhuang Mao Png, Teck Lip Dexter Tam, Qiang Zhu, David John Procter, Jianwei Xu
Summary: A new PPyD electron acceptor was synthesized via the Diels Alder reaction and used to construct five donor-acceptor type conjugated polymers. The study showed that the polymers exhibit multiple colors in the neutral state and switch to different colors upon applying voltage. This work demonstrates the potential of PPyD acceptor for electrochromic conjugated polymers and other organic electronics.
Article
Multidisciplinary Sciences
Xiaojie Shi, Yue Wan, Nan Wang, Jiangchao Xiang, Tao Wang, Xiaofeng Yang, Ju Wang, Xuxue Dong, Liang Dong, Lei Yan, Yu Li, Lili Liu, Shinchen Hou, Zhenwei Zhong, Ian A. Wilson, Bei Yang, Guang Yang, Richard A. Lerner
Summary: This study presents an epitope-guided method for selecting antibodies that modulate cellular signaling of targeted receptors, focusing on the G-protein coupled receptor CXCR2. The obtained antibody shows potential for therapeutic development in diseases involving inappropriate neutrophil migration. The antibody targets the chemokine receptor and competes with natural ligand, blocking neutrophil chemotaxis and protecting mice in an EAE model.
NATURE COMMUNICATIONS
(2021)
Article
Fisheries
Beibei Zhao, Jing Diao, Le Li, Hidehiro Kondo, Lei Li, Ikuo Hirono
Summary: This study identified and characterized the CXCR2 gene in Japanese flounder, showing that the expression levels of JfCXCR1 and JfCXCR2 increase significantly in response to bacterial infections, with JfCXCR1 potentially activated by bacterial infections and JfCXCR2 activated by both bacterial and viral infections to mediate the immune response. These findings contribute to understanding the functions of CXCR1 and CXCR2 in the fish immune system.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Max Van Hoof, Sandra Claes, Katrijn Boon, Tom Van Loy, Dominique Schols, Wim Dehaen, Steven De Jonghe
Summary: Upregulated CXCR2 signalling is common in inflammatory, autoimmune, neurodegenerative diseases, and cancer, making CXCR2 antagonism a promising therapeutic strategy. Previous research identified a pyrido[3,4-d]pyrimidine analogue as a potent CXCR2 antagonist. This study aims to improve the CXCR2 antagonistic potency through structural modifications, but most new analogues lacked CXCR2 antagonism except for a 6-furanyl-pyrido[3,4-d]pyrimidine analogue.
Article
Medicine, General & Internal
Anthony C. Gordon, Farah Al-Beidh, Kathryn M. Rowan, Alistair D. Nichol, Yaseen M. Arabi, Djillali Annane, Ahi Beane, Wilma Van Bentum-Puijk, Lindsay R. Berry, Zahra Bhimani, Marc J. M. Bonten, Charlotte A. Bradbury, Frank M. Brunkhorst, Adrian Buzgau, Allen C. Cheng, Michelle A. Detry, Eamon J. Duffy, Lise J. Estcourt, Mark Fitzgerald, Herman Goossens, Rashan Haniffa, Alisa M. Higgins, Thomas E. Hills, Christopher M. Horvat, Francois Lamontagne, Patrick R. Lawler, Helen L. Leavis, Kelsey M. Linstrum, Edward Litton, Elizabeth Lorenzi, John C. Marshall, Florian B. Mayr, Daniel F. McAuley, Anna McGlothlin, Shay P. McGuinness, Bryan J. McVerry, Stephanie K. Montgomery, Susan C. Morpeth, Srinivas Murthy, Katrina Orr, Rachael L. Parke, Jane C. Parker, Asad E. Patanwala, Ville Pettill, Emma Rademaker, Marlene S. Santos, Christina T. Saunders, Christopher W. Seymour, Manu Shankar-Hari, Wendy L. Sligl, Alexis F. Turgeon, Anne M. Turner, Frank L. van de Veerdonk, Ryan Zarychanski, Cameron Green, Roger J. Lewis, Derek C. Angus, Colin J. McArthur, Scott Berry, Steve A. Webb, Lennie P. G. Derde
Summary: Interleukin-6 receptor antagonists tocilizumab and sarilumab were found to improve outcomes, including survival, in critically ill patients with Covid-19 receiving organ support in ICUs according to an ongoing international trial. The efficacy of these treatments has been confirmed, with patients benefiting from the therapy.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Biology
Ho Tsoi, Ling Shi, Man-Hong Leung, Ellen P. S. Man, Zi-Qing So, Wing-Lok Chan, Ui-Soon Khoo
Summary: A splice variant of NCOR2, called BQ, enhances tamoxifen resistance in ER+ breast cancer cells by modulating IL-8 expression. Targeting IL-8 signaling pathway is a promising approach to overcome tamoxifen resistance in ER+ breast cancer.
Article
Fisheries
Zihao Zhao, Hao Peng, Tao Han, Zhijing Jiang, Jieyi Yuan, Xue Liu, Xiaoqian Wang, Yuexing Zhang, Tianming Wang
Summary: From transcriptomic data of largemouth bass, an IL8R highly homologous to teleost IL-8Rs was identified. Phylogenetic analysis compared M. salmoides IL-8 receptor (MsCXCR2) with the C-X-C motif chemokine receptor 2 subfamily. Results showed activation of MsCXCR2 by LcIL-8, internalization of the receptor, and ERK phosphorylation. Constitutive expression of MsCXCR2 in examined tissues, with significant upregulation in the liver and head kidney of diseased fish, was observed.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Adeline Blandinieres, Xuechong Hong, Aurelien Philippe, Ivan Bieche, Sophie Vacher, Elisa Rossi, Gregoire Detriche, Nicolas Gendron, Pascale Gaussem, Coralie L. Guerin, Juan M. Melero-Martin, David M. Smadja
Summary: Studies have investigated the presence of CXCR1 and CXCR2 receptors on ECFCs, finding that these receptors were not detected. In addition, comparison of RT-PCR primers used to search for CXCR1 and CXCR2 mRNA revealed potential non-specific DNA amplification.
STEM CELL REVIEWS AND REPORTS
(2021)
Review
Oncology
Jan Korbecki, Patrycja Kupnicka, Katarzyna Barczak, Mateusz Bosiacki, Pawel Zietek, Dariusz Chlubek, Irena Baranowska-Bosiacka
Summary: AML is a type of leukemia with a poor prognosis. This review focuses on the significance of CXC chemokines other than CXCL12 in AML, including their roles in AML tumor processes, clinical relevance, and association with other factors such as chemoresistance and bone marrow angiogenesis. The aim of this study is to provide an overview of the less-studied CXC chemokine axes in AML and bridge the gap in current research.
Article
Endocrinology & Metabolism
Lorenzo Piemonti, Bart Keymeulen, Pieter Gillard, Thomas Linn, Emanuele Bosi, Ludger Rose, Paolo Pozzilli, Francesco Giorgino, Efisio Cossu, Luisa Daffonchio, Giovanni Goisis, Pier Adelchi Ruffini, Anna Rita Maurizi, Flavio Mantelli, Marcello Allegretti
Summary: The study aimed to evaluate the effects of ladarixin (LDX) on sustaining C-peptide production in newly diagnosed type 1 diabetes patients. The results showed that short-term LDX treatment had no significant impact on preserving residual beta cell function, but there were transient metabolic benefits in some secondary endpoints.
DIABETES OBESITY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Thi-Thuy-Nga Tran, Que-Huong Tran, Cuong Quoc Duong, Quoc-Thai Nguyen, Van-Thanh Tran, Minh-Tri Le, Viet-Hung Tran, Khac-Minh Thai
Summary: This study aimed to discover novel CXCR2 antagonists to block the IL-8 signaling pathway using in silico drug design. A structure-based pharmacophore model was developed based on the crystal structure of CXCR2 and validated, followed by virtual screening and molecular docking. Seven compounds were selected based on their interaction potential, efficacy, and safety. Molecular dynamics simulations confirmed the stability of the protein-ligand complex structure. It was identified that ZINC77105530 and ZINC93176465 were potential inhibitors of IL-8 signaling pathways.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Xin Zhong, Xueying Zhao, Liyuan Zhang, Ning Liu, Sa Shi, Yuwen Wang
Summary: This study found that the donor of hydrogen sulfide, sodium hydrosulfide, can inhibit endothelial cell injury and neutrophil activation in type 1 diabetes mellitus rats through the IL-8/CXCR2/ROS/NF-kappa B axis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Mariola Napiorkowska, Dagmara Kurpios-Piec, Ewelina Kiernozek-Kalinska, Anna Lesniak, Malgorzata Klawikowska, Magdalena Bujalska-Zadrozny
Summary: This study developed new antitumor agents by combining compounds containing dicarboximide skeleton and the piperazine ring. The compounds showed significant activity against cancer cells and had weaker cytotoxic effects on normal cells. The functional activities at different receptors were also determined for these compounds.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
