Article
Biochemistry & Molecular Biology
Claudia Vergelli, Andrei I. Khlebnikov, Letizia Crocetti, Gabriella Guerrini, Niccolo Cantini, Liliya N. Kirpotina, Igor A. Schepetkin, Agostino Cilibrizzi, Mark T. Quinn, Patrizia Rossi, Paola Paoli, Maria Paola Giovannoni
Summary: N-formyl peptide receptors (FPR1, FPR2, and FPR3) have important roles in regulating inflammatory processes and cancer progression. New pyrazole and pyrazolone derivatives showed low or absent FPR agonist activity, indicating that the five-membered scaffold was not suitable for FPR agonists. Molecular modeling studies confirmed that the four-membered scaffold was essential for better arrangement of molecules in the receptor binding site.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Chemistry, Medicinal
Nicholas R. Wurtz, James A. Johnson, Andrew Viet, Pravin S. Shirude, Vishweshwaraiah Baligar, Sudhakara Madduri, Daniel L. Cheney, Hyunsoo Park, John A. Lupisella, Mei-Yin Hsu, Mojgan Abousleiman, Michael A. Galella, Darpandeep Aulakh, Elizabeth A. Dierks, Ricardo A. Garcia, Jacek Ostrowski, Ellen K. Kick, Ruth R. Wexler
Summary: In this study, we discovered benzimidazole and aminophenyloxadiazole FPR2 agonists with low nanomolar activity. Our findings demonstrate the significant impact of electronic effects of heteroatom placement on molecular recognition.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Letizia Crocetti, Claudia Vergelli, Gabriella Guerrini, Maria Paola Giovannoni, Liliya N. Kirpotina, Andrei Khlebnikov, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Elena Lucarini, Igor A. Schepetkin, Mark T. Quinn
Summary: Research has shown the potential value of N-formyl peptide receptors for the treatment of rheumatoid arthritis, with demonstrated efficacy in animal models. Further studies on pyridinone derivatives, supported by molecular modeling and pharmacological tests in rat models, have shown promising biological results.
Article
Biochemistry & Molecular Biology
Itzia S. Gomez-Alonso, Sergio Martinez-Garcia, Gabriel Betanzos-Cabrera, Esmeralda Juarez, Maria C. Sarabia-Leon, Maria Teresa Herrera, Fernando Gomez-Chavez, Luvia Sanchez-Torres, Sandra Rodriguez-Martinez, Mario E. Cancino-Diaz, Jorge Cancino, Juan C. Cancino-Diaz
Summary: Protease-3 released by neutrophils in the presence of commensal non-biofilm-forming S. epidermidis plays a key role in promoting biofilm formation by facilitating cell aggregation through the release of bacterial DNA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hsiang-Ruei Liao, Chin-Hsuan Lin, Jih-Jung Chen, Fu-Chao Liu, Ching-Ping Tseng
Summary: Epsilon-viniferin inhibits the respiratory burst induced by fMLP in human neutrophils by antagonizing formyl peptide receptor 1 in a reversible and non-competitive manner.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Pharmacology & Pharmacy
Huamei Forsman, Yanling Wu, Jonas Martensson, Lena Bjorkman, Kenneth L. Granberg, Claes Dahlgren, Martina Sundqvist
Summary: Formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor that recognizes short N-formylated peptides. The recently discovered FPR1 antagonist AZ2158 is a potent inhibitor of neutrophil chemotaxis and can act on both balanced and biased FPR1 agonists. This compound shows promise for further study of FPR1-mediated activities.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Immunology
Runa Kuley, Bhargavi Duvvuri, Jeffrey J. Wallin, Nam Bui, Mary Vic Adona, Nicholas G. O'Connor, Sharon K. Sahi, Ian B. Stanaway, Mark M. Wurfel, Eric D. Morrell, W. Conrad Liles, Pavan K. Bhatraju, Christian Lood
Summary: Neutrophil dysregulation is a recognized feature of COVID-19, but the factors contributing to neutrophil activation in this disease are not well understood. This study found elevated levels of calprotectin, neutrophil extracellular traps (NETs), and N-formyl methionine (fMet) in COVID-19 patients, particularly in critically ill patients. The levels of NETs were higher in ICU patients with COVID-19 compared to ICU patients without COVID-19, suggesting a significant contribution of NETs in COVID-19. In vitro experiments showed that plasma from COVID-19 patients induced neutrophil activation through fMet/FPR1-dependent mechanisms. The study concludes that fMet is an important factor contributing to neutrophil activation in COVID-19 and may be a potential target for therapeutic intervention.
Article
Virology
Yueyuan Shi, Xin Jin, Shuang Wu, Junye Liu, Hongpeng Zhang, Xuefei Cai, Yuan Yang, Xiang Zhang, Jie Wei, Miao Luo, Hua Zhou, Huihao Zhou, Ailong Huang, Deqiang Wang
Summary: In this study, the mechanism of hepatitis B virus (HBV) enveloped particle release was investigated. Glucose-regulated protein (GRP)78 was identified as a specific binding target for preS1, and its interaction with preS1 was found to positively regulate the release of HBV-enveloped particles. Additionally, peptides inhibiting enveloped-particle release were identified as potential therapeutic agents for inhibiting HBV infection.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Chemistry, Medicinal
Joshua T. Mattila, Wissam Beaino, Alexander G. White, Lea Nyiranshuti, Pauline Maiello, Jaime Tomko, L. James Frye, Daniel Fillmore, Charles A. Scanga, Philana Ling Lin, JoAnne L. Flynn, Carolyn J. Anderson
Summary: Neutrophilic inflammation is associated with severe tuberculosis caused by Mycobacterium tuberculosis. A specific PET probe targeting neutrophils has been tested in macaques, showing correlation with granulomas and potential applications in TB imaging but with some issues to be addressed before human use.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Svetlana I. I. Galkina, Ekaterina A. A. Golenkina, Marina V. V. Serebryakova, Natalia V. V. Fedorova, Alexander L. L. Ksenofontov, Vladimir I. I. Stadnichuk, Galina F. F. Sud'ina
Summary: The study found that ivermectin has an inhibitory effect on neutrophil adhesion and secretion, possibly reducing cell invasion into tissue by suppressing the release of hydroxylysine, while promoting the release of phenylalanine and cathepsin G. Additionally, the experiment suggested the potential involvement of ivermectin in the inactivation of angiotensin II.
Article
Cell Biology
Andrea I. d'Aquino, Caitlin L. Maikawa, Leslee T. Nguyen, Katie Lu, Ian A. Hall, Carolyn K. Jons, Catherine M. Kasse, Jerry Yan, Alexander N. Prossnitz, Enmian Chang, Sam W. Baker, Lars Hovgaard, Dorte B. Steensgaard, Hanne B. Andersen, Lotte Simonsen, Eric A. Appel
Summary: This study developed a drug product capable of delivering GLP-1 RA for months using an injectable hydrogel depot technology. The therapy sustained GLP-1 RA exposure for 42 days in a rat model, equivalent to once-every-4-months treatment in humans. Compared to daily injections, this hydrogel therapy effectively maintains blood glucose and weight management.
CELL REPORTS MEDICINE
(2023)
Review
Chemistry, Applied
Luis Pena Icart, Fernando Gomes Souza Jr, Luis Mauricio T. R. Lima
Summary: Type 2 diabetes is a fast-growing worldwide epidemic, but over half of patients do not manage the disease correctly due to non-compliance with treatment regimes. The development of analogues to GLP-1 and the use of controlled-release systems have brought new hopes for treating type 2 diabetes.
JOURNAL OF MICROENCAPSULATION
(2021)
Article
Oncology
Xiangqian Guan, Yuyan Lu, Heping Zhu, Shuqi Yu, Wenxiu Zhao, Xiaoqin Chi, Chengrong Xie, Zhenyu Yin
Summary: This study revealed that the release of NETs is increased in HCC patients, especially those with portal vein tumor thrombosis. The presence of NETs in HCC tumor tissues is closely associated with a poor prognosis. Functionally, co-culture of HCC neutrophils enhances the invasion ability of HCC cells through NETs formation, while neutrophils from healthy donors inhibit invasion ability. Mechanistic investigations showed that HCC cells-derived cytokine IL-8 triggers NADPH oxidase-dependent NETs formation, promoting HCC metastasis in vitro and in vivo.
JOURNAL OF HEPATOCELLULAR CARCINOMA
(2021)
Article
Biochemistry & Molecular Biology
Marta Alonso-Gardon, Xabier Elorza-Vidal, Aida Castellanos, Gina La Sala, Mercedes Armand-Ugon, Alice Gilbert, Chiara Di Pietro, Adria Pla-Casillanis, Francisco Ciruela, Xavier Gasull, Virginia Nunes, Albert Martinez, Uwe Schulte, Martine Cohen-Salmon, Daniela Marazziti, Raul Estevez
Summary: MLC is a vacuolating leukodystrophy primarily caused by mutations in MLC1 or GLIALCAM genes, with the brain GlialCAM interacting proteome involving various proteins related to brain homeostasis regulation, including G protein-coupled receptors.
HUMAN MOLECULAR GENETICS
(2021)
Article
Immunology
Jun Liu, Shuoya Huang, Ruoxun Yu, Xinwei Chen, Fanying Li, Xin Sun, Pengyang Xu, Yijia Huang, Yunxia Xue, Ting Fu, Zhijie Li
Summary: TRPV1(+) sensory nerves control inflammation and recruitment, and promote corneal wound healing via RAMP1 and SSTR5 signaling.
MUCOSAL IMMUNOLOGY
(2022)