Article
Pediatrics
Yilin Dong, Chunfang Jin, Zhiqiang Ding, Yiting Zhu, Qian He, Xinxin Zhang, Rongshuang Ai, Yibing Yin, Yujuan He
Summary: This study found that autophagy and ROS are required for S.pn-induced NETs formation in the model of acute otitis media (AOM). TLR4 partially mediated NETs formation during AOM. The research may provide a potential strategy for the treatment of otitis media.
PEDIATRIC RESEARCH
(2021)
Article
Immunology
Ming Li, Yabing Gao, Zhenglei Wang, Binfeng Wu, Jinqiu Zhang, Yuanyuan Xu, Xiangan Han, Vanhnaseng Phouthapane, Jinfeng Miao
Summary: This study investigated the molecular mechanisms of S. uberis-induced NETs formation and the regulatory role of taurine. The results showed that taurine can protect mammary epithelial cells and barriers from damage by reducing S. uberis-induced NETs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jennifer L. Johnson, Elsa Meneses-Salas, Mahalakshmi Ramadass, Jlenia Monfregola, Farhana Rahman, Raquel Carvalho Gontijo, William B. Kiosses, Kersi Pestonjamasp, Dale Allen, Jinzhong Zhang, Douglas G. Osborne, Yanfang Peipei Zhu, Nathan Wineinger, Kasra Askari, Danni Chen, Juan Yu, Scott C. Henderson, Catherine C. Hedrick, Matilde Valeria Ursini, Sergio Grinstein, Daniel D. Billadeau, Sergio D. Catz
Summary: This study investigates the process of exocytosis in neutrophil leukocytes and shows that the actin nucleator protein WASH plays a critical role in this process. The authors find that WASH facilitates the release of gelatinase granules while inhibiting the release of pro-inflammatory granules. They also discover that a deficiency in WASH leads to dysregulated secretion and inflammation in neutrophil leukocytes.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Heather A. Parker, Harry M. Jones, Christopher D. Kaldor, Mark B. Hampton, Christine C. Winterbourn
Summary: Neutrophils release extracellular traps (NETs) in response to various stimuli, involving an oxidative mechanism and the activities of NADPH oxidase (NOX2) and myeloperoxidase (MPO). NOX2 inhibitor DPI significantly inhibits NET formation, even when added post-stimulation, indicating a late-stage requirement for oxidant production. MPO activity plays a crucial role in NET induction with some stimuli, but not all, suggesting multiple oxidant-dependent steps in the process.
Article
Immunology
Daniel E. Hammers, Deborah L. Donahue, Zachary D. Tucker, Brandon L. Ashfeld, Victoria A. Ploplis, Francis J. Castellino, Shaun W. Lee
Summary: This study reveals that the Streptolysin S (SLS) of Group A Streptococcus (GAS) targets the electroneutral sodium-bicarbonate cotransporter NBCn1 in keratinocytes, inducing NF-kappa B activation and host cytotoxicity. SLS also disrupts the ability of host cells to regulate their intracellular pH.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Cell Biology
Marie-Helene Paclet, Salome Laurans, Sophie Dupre-Crochet
Summary: This article reviews the multiple roles of NOX2 in neutrophil functions, with a focus on the description of its components and their assembly mechanisms. It also explains the role of energy metabolism and phosphoinositides in regulating NADPH oxidase activity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Medicine, General & Internal
Jean-Paul Cristol, Alain R. Thierry, Anne-Sophie Bargnoux, Marion Morena-Carrere, Bernard Canaud
Summary: Despite progress in dialysis modalities, intermittent renal replacement therapy remains imperfect in correcting uremic disorders and may lead to low-grade chronic inflammation and oxidative stress. Understanding dialysis bioincompatibility pathways is still a challenge, as current biomarkers cannot distinguish all components involved in these complex pathways.
FRONTIERS IN MEDICINE
(2023)
Correction
Immunology
Fatma Tannich, Asma Tlili, Coralie Pintard, Amina Chniguir, Bruno Eto, Pham My-Chan Dang, Ouajdi Souilem, Jamel El-Benna
Summary: The same mouse brain extracts were used in both figures to ensure accuracy in the study results.
INFLAMMOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Minoru Inoue, Masahiro Enomoto, Michio Yoshimura, Takashi Mizowaki
Summary: The study shows that inhibition of Na+/Ca2+ exchange by EIPA and MIA can trigger NETotic cell death in neutrophils, indicating a new mechanism of infection-independent NET generation.
Article
Biochemistry & Molecular Biology
Napissara Boonpraman, Sunmi Yoon, Chae Young Kim, Jong-Seok Moon, Sun Shin Yi
Summary: Oxidative stress and mitochondrial dysfunction play an important role in aging and neurodegenerative diseases, such as Parkinson's disease (PD). NOX4, a member of the NOX family, is associated with PD progression. In this study, we found that the hippocampus had elevated levels of NOX4 and α-synuclein during PD, and neuroinflammatory cytokines MPO and OPN were upregulated in astrocytes. Furthermore, upregulation of MPO and OPN induced mitochondrial dysfunction and ferroptosis in human astrocytes. Overall, our findings suggest that NOX4 cooperates with MPO and OPN to induce mitochondrial aberration in hippocampal astrocytes during PD.
Review
Pharmacology & Pharmacy
Huamei Forsman, Claes Dahlgren, Jonas Martensson, Lena Bjorkman, Martina Sundqvist
Summary: Human neutrophils, as professional phagocytes, express several G protein-coupled receptors (GPCRs) that are essential for their functions. Recently, the FFA receptors, GPR84 and FFA2, have attracted attention for their involvement in neutrophil activation. This review summarizes the current understanding of how GPR84 affects human neutrophil functions and discusses the regulatory mechanisms, comparing them to the two FPRs and FFA2.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chihiro Aikawa, Kiyosumi Kawashima, Chihiro Fukuzaki, Makoto Nakakido, Kazunori Murase, Takashi Nozawa, Kouhei Tsumoto, Ichiro Nakagawa
Summary: Group A Streptococcus causes various diseases, with toxins like streptolysin O playing a key role in severe infections. Research has identified an anti-SLO single-chain variable fragment, SLO-I4, which effectively inhibits GAS-induced cell lysis and may be beneficial in combating GAS infections.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Microbiology
Takashi Nozawa, Junpei Iibushi, Hirotaka Toh, Atsuko Minowa-Nozawa, Kazunori Murase, Chihiro Aikawa, Ichiro Nakagawa
Summary: Group A Streptococcus (GAS) disrupts the Golgi complex in host cells by secreting SLO and Nga, impacting anterograde transport in infected cells and affecting the integrity of the epithelial barrier and immune response. The invasion of GAS is associated with the virulence exerted by SLO and Nga, highlighting a previously unknown bacterial invasion-dependent function of Nga and GAS-host interaction.
Article
Materials Science, Biomaterials
Mousumi Baruah, Anal Jana, Mudassar Ali, Koyeli Mapa, Animesh Samanta
Summary: The innate immune system eliminates pathogens through phagocytosis and the production of reactive oxygen species (ROS), such as the pro-inflammatory oxidant hypochlorous acid (HOCl). This study developed a pentacyclic pyridinium probe, PM-S, to efficiently detect HOCl in the Nox2 pathway. The probe showed advantages in terms of stability, sensitivity, and specificity to mitochondria, providing a novel platform for monitoring the inflammatory process.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Lanqiu Zhang, Hejun Gao, Lei Yang, Tianyu Liu, Qi Zhang, Jing Xun, Caixia Li, Lihua Cui, Ximo Wang
Summary: FTY720 has the potential to induce the formation of neutrophil extracellular traps (NETs) in vitro, which involves autophagy and the activation of p38 and AKT. Citrullination of histone H3 and peptidylarginine deiminase 4 (PAD4) are not required for FTY720-induced NET formation, while necroptosis signaling activation is involved in the process.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Immunology
Dylan Minor, Jacob Cavon, Thea Johnson, Savannah Ontiveros, Daniel Gao, Mark T. Quinn, Benfang Lei
Summary: In this study, we investigated whether MyD88 KO mice were susceptible to acute group A Streptococcus (GAS) infection through transmission. We found that MyD88(-/-) recipient mice had increased GAS loads in the nasal cavity and throat and became moribund after commingling with GAS-infected mice. Furthermore, we observed that MyD88 signaling is critical for protection of the respiratory tract lamina propria but not nasal and nasopharyngeal epithelia against GAS infection.
INFECTION AND IMMUNITY
(2022)
Article
Chemistry, Multidisciplinary
Nikolay N. Zolotov, Igor A. Schepetkin, Tatyana A. Voronina, Vladimir F. Pozdnev, Andrei Khlebnikov, Irina Krylova, Mark T. Quinn
Summary: This study characterized five novel compounds that are potent inhibitors of POP and can penetrate the blood-brain barrier. Experimental results showed that four of these compounds have anti-amnesic effects in animal models, and indicate an important role of POP in the regulation of learning and memory processes in the central nervous system.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Margherita Mastromarino, Maria Favia, Igor A. Schepetkin, Lylia N. Kirpotina, Ewa Trojan, Mauro Niso, Antonio Carrieri, Monika Leskiewicz, Magdalena Regulska, Massimiliano Darida, Francesco Rossignolo, Stefano Fontana, Mark T. Quinn, Agnieszka Basta-Kaim, Marcello Leopoldo, Enza Lacivita
Summary: Formyl peptide receptor 2 (FPR2) agonists, including the newly identified ureidopropanamide derivatives, show promising potential in resolving inflammation and treating neurodegenerative disorders with underlying chronic neuroinflammation. Computational studies provide insights into the interactions between these compounds and FPR2. In vitro and in vivo experiments demonstrate the anti-inflammatory effects and improved mitochondrial function of selected compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Niccolo Cantini, Letizia Crocetti, Gabriella Guerrini, Claudia Vergelli, Silvia Lamanna, Igor A. Schepetkin, Marco Pallecchi, Gianluca Bartolucci, Andrei Khlebnikov, Mark T. Quinn, Patrizia Rossi, Paola Paoli, Maria Paola Giovannoni
Summary: This study developed potent inhibitors of human neutrophil elastase (HNE) using a classic medicinal chemistry approach starting from previously published pyrazolocyclohexanone compounds. By modifying the cyclohexanone ring, pyrazolocyclopentanone and pyrazolocycloheptanone derivatives were obtained. Both derivatives showed potent inhibitory activity against HNE in the nanomolar range, with the activity dependent on the presence of an N-CO function. Spectroscopic techniques and crystallographic studies were used to confirm the structures of the obtained isomers. Molecular modeling of the most active compound demonstrated its favorable orientation for inhibitory activity.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Materials Science, Multidisciplinary
Nadezhda V. Danilenko, Evgeny N. Bolbasov, Andrei I. Khlebnikov, Igor A. Schepetkin, Sergei I. Tverdokhlebov, Mark T. Quinn
Summary: The development of bioresorbable scaffolds with anticancer properties is important for tissue repair after surgical resection of tumors. Naphthoquinones show high anticancer activity and have potential for creating effective scaffolds. In this study, electrospun polycaprolactone (PCL) scaffolds embedded with different concentrations of 2-chloro-3-((4-hydroxyphenyl)amino)-1,4-naphthoquinonone (NQCP4) were fabricated and showed enhanced anticancer properties with increasing NQCP4 concentrations.
Article
Pharmacology & Pharmacy
Igor A. Schepetkin, Anastasia R. Kovrizhina, Ksenia S. Stankevich, Andrei I. Khlebnikov, Liliya N. Kirpotina, Mark T. Quinn, Matthew J. Cook
Summary: This study synthesized a panel of novel tryptanthrin oxime analogs and evaluated their binding affinity to JNK1-3 and inhibition of cellular inflammatory responses. Compound 1j exhibited high binding affinity to JNK1-3 and demonstrated anti-inflammatory activity by inhibiting the production of multiple proinflammatory cytokines. Molecular modeling confirmed the binding mode of 1j to JNK3.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Igor A. Schepetkin, Galina A. Chernysheva, Oleg Aliev, Liliya N. Kirpotina, Vera Smol'yakova, Anton N. Osipenko, Mark B. Plotnikov, Anastasia R. Kovrizhina, Andrei Khlebnikov, Evgenii Plotnikov, Mark T. Quinn
Summary: The synthesized IQ-1L lithium salt is a more effective JNK inhibitor compared to IQ-1S, showing better anti-inflammatory activity and neuroprotective effects.
Review
Immunology
Scott D. Kobayashi, Frank R. DeLeo, Mark T. Quinn
Summary: Neutrophils are an important component of innate host defense, with a high production rate and rapid mobilization to infected tissues. They contain abundant antimicrobial molecules, but their turnover and activation are tightly regulated. Microbial pathogens can affect the apoptosis and cytolysis of neutrophils, altering their function.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Plant Sciences
Igor A. Schepetkin, Gulmira Ozek, Temel Ozek, Liliya N. Kirpotina, Polina Kokorina, Andrei Khlebnikov, Mark T. Quinn
Summary: This study found that essential oils from black poplar and propolis, as well as nerolidol, can modulate the immune response and chemotaxis of human neutrophils.
Article
Biochemistry & Molecular Biology
Igor A. Schepetkin, Zhangeldy S. Nurmaganbetov, Serik D. Fazylov, Oralgazy A. Nurkenov, Andrei I. Khlebnikov, Tulegen M. Seilkhanov, Anarkul S. Kishkentaeva, Elvira E. Shults, Mark T. Quinn
Summary: Alzheimer's disease is a common neurodegenerative disease characterized by memory loss and cognitive impairment. The loss of cholinergic neurons is one of the main causes of this disease. Current acetylcholinesterase inhibitors have limitations, so there is ongoing research to find more effective inhibitors. In this study, new lupinine triazole derivatives were synthesized and evaluated for their inhibitory activity. The most promising compound showed mixed-type inhibition and molecular docking studies revealed the interaction between the compound and the target enzyme. A structure-activity relationship model was also developed to guide the design of more potent inhibitors.
Article
Biochemistry & Molecular Biology
Igor A. Schepetkin, Oleksander S. Karpenko, Anastasia R. Kovrizhina, Liliya N. Kirpotina, Andrei I. Khlebnikov, Stepan I. Chekal, Alevtyna V. Radudik, Maryna O. Shybinska, Mark T. Quinn
Summary: The JNK family, including JNK1-3 proteins, regulates various physiological processes. The study aimed to find JNK inhibitors with high selectivity for JNK3. 26 new tryptanthrin-6-oxime analogs were synthesized and evaluated, and compounds 4d and 4e showed high selectivity for JNK3 and inhibited inflammatory responses. The results suggest the potential for developing anti-inflammatory drugs with selectivity for JNK3.
Article
Plant Sciences
Igor A. Schepetkin, Gulmira Ozek, Temel Ozek, Liliya N. Kirpotina, Robyn A. Klein, Andrei I. Khlebnikov, Mark T. Quinn
Summary: Analysis of essential oils extracted from Agastache urticifolia, Achillea millefolium, and Perideridia gairdneri showed that they can activate human neutrophils with varying efficacy, indicating their immunomodulatory activity.
Article
Chemistry, Medicinal
Mark B. Plotnikov, Galina A. Chernysheva, Vera I. Smol'yakova, Oleg I. Aliev, Anna M. Anishchenko, Olga A. Ulyakhina, Eugene S. Trofimova, Anastasia A. Ligacheva, Nina D. Anfinogenova, Anton N. Osipenko, Anastasia R. Kovrizhina, Andrei I. Khlebnikov, Igor A. Schepetkin, Anastasia G. Drozd, Evgenii V. Plotnikov, Dmitriy N. Atochin, Mark T. Quinn
Summary: The study aimed to investigate the neuroprotective effects of TRYP-Ox in a rat model of transient focal cerebral ischemia. The results showed that TRYP-Ox could alleviate neurological deficits, decrease infarction size, inhibit inflammation, and exhibit antioxidant activity, suggesting that it may be a promising neuroprotective agent.
Article
Chemistry, Medicinal
Fabio Francavilla, Federica Sarcina, Igor A. Schepetkin, Lilya N. Kirpotina, Marialessandra Contino, Annalisa Schirizzi, Giampiero De Leonardis, Andrei I. Khlebnikov, Rosalba D'Alessandro, Mark T. Quinn, Enza Lacivita, Marcello Leopoldo
Summary: FPR1 is expressed in tumor cells and plays a role in tumor growth and invasiveness. A new series of compounds with potent FPR1 antagonist activity has been designed, which can inhibit cell growth by regulating cell proliferation, apoptosis, and migration.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)