Article
Microbiology
Hasnaa Maksouri, Dounia Darif, Jerome Estaquier, Myriam Riyad, Christophe Desterke, Meryem Lemrani, Pham My-Chan Dang, Khadija Akarid
Summary: This study evaluated the impact of Moroccan strains of L. major and L. tropica on PMNs. The results showed that L. tropica inhibited O-2(-) production, while L. major did not. Additionally, Leishmania soluble antigens from both species inhibited O-2(-) induction.
Article
Chemistry, Medicinal
Jie Zang, Felix Peters, Yves Cambet, Eugenia Cifuentes-Pagano, Munira Mohamed Shishay Hissabu, Christopher M. Dustin, Lars Henrik Svensson, Martin Mariboe Olesen, Mathias Feldt Lomholt Poulsen, Stig Jacobsen, Pernille Sonderby Tuelung, Dilip Narayanan, Annette Eva Langkilde, Michael Gajhede, Patrick J. Pagano, Vincent Jaquet, Frederik Vilhardt, Anders Bach
Summary: In this study, we optimized and explored bivalent small-molecule drugs targeting the NOX2 subunit p47phox and identified compounds with high binding affinities and cellular activities, demonstrating the potential of p47phox as an effective small-molecule target. This has important implications for the research and development of therapeutic drugs for related diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Cell Biology
Daniel Simoes de Jesus, Paula Bargi-Souza, Vinicius Cruzat, Vijay Yechoor, Angelo Rafael Carpinelli, Rodrigo Antonio Peliciari-Garcia
Summary: The pancreatic beta cells circadian clock and NADPH oxidase (NOX) family play important roles in glucose metabolism. Absence of BMAL1 may trigger an increase in NOX2-derived reactive oxygen species (ROS) in pancreatic beta cells, leading to inhibition of insulin secretion.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Anthony L. Sylvester, David X. Zhang, Sophia Ran, Natalya S. Zinkevich
Summary: Reactive oxygen species (ROS) play important roles in health and disease, with both beneficial and harmful effects. Different sources of ROS have different roles in various pathologies. NOX1 is associated with hypertension through ROS production, making it a promising therapeutic target. NOX2 and NOX4 produce hydrogen peroxide, influencing cellular processes. Increased ROS production from NOX5 contributes to atherosclerosis.
Article
Biochemistry & Molecular Biology
Hana Valenta, Sophie Dupre-Crochet, Mouna Abdesselem, Tania Bizouarn, Laura Baciou, Oliver Nusse, Ariane Deniset-Besseau, Marie Erard
Summary: The phagocyte NADPH oxidase is a key enzyme of the innate immune system, and the use of the chimeric protein Trimera can activate the enzyme and sustain high levels of activity, but it leads to intracellular acidification, apoptosis, and local peroxidation of lipids in the membrane.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Agronomy
Jie Li, Lidan Feng, Dong Li, Xianglin Liu, Yangyang Pan, Jing He, Junxia Zhang
Summary: This study investigates the role of ROS mediated by NADPH oxidase in the growth of F. solani. The results demonstrate that NCF2 gene plays a significant role in regulating the activity of NADPH oxidase and the expression of ROS metabolism enzyme genes, which affects colony growth in F. solani. Furthermore, exogenous H2O2 treatment also influences the growth and ROS metabolism of F. solani.
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)
Article
Cardiac & Cardiovascular Systems
Yuanyuan Cao, Zhangwei Chen, Jianguo Jia, Ao Chen, Yanhua Gao, Juying Qian, Junbo Ge
Summary: The study found that rosuvastatin mitigates coronary microembolism (CME)-induced cardiac injury by inhibiting Nox2-induced ROS overproduction and alleviating p53/Bax/Bcl-2-dependent cardiomyocyte apoptosis.
CARDIOVASCULAR TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jose L. Martin, Aaqil Khan, Elena E. Grintsevich
Summary: Mical family enzymes are unique regulators of actin that promote filament disassembly and hydrogen peroxide generation. The intrinsic dynamics of Mical-oxidized actin isoforms vary, which is related to the patterns of hydrogen peroxide generation. Furthermore, actin stabilization is linked to the activation of MICALs' NADPH oxidase activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dezhen Tu, Ravikanth Velagapudi, Yun Gao, Jau-Shyong Hong, Hui Zhou, Hui-Ming Gao
Summary: This study investigates the expression patterns, regulatory mechanisms, and pathological roles of neuronal NADPH oxidase in inflammation-associated neurodegeneration. The results show that NOX2 is persistently upregulated in neurons during chronic neuroinflammation and is associated with oxidative stress and neurodegeneration. Inhibition of neuronal NOX2 can block the degenerative effects of inflammatory mediators and prevent neurodegeneration.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Immunology
Yingze Ye, Zhihong Jian, Tong Jin, Yina Li, Zhi Zeng, Xu Zhang, Xiaoxing Xiong, Lijuan Gu
Summary: This study suggests that NADPH oxidase 2 (NOX2)-mediated reactive oxygen species (ROS) production exacerbates acute brain injury but promotes functional recovery after stroke. Inhibiting NOX2 activity can reduce infarct size and mortality, but may hinder functional recovery. This effect may be related to neuroinflammation, autophagy, angiogenesis, and the PI3K/Akt signaling pathway.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Carla Ijurko, Marta Romo-Gonzalez, Clara Garcia-Calvo, Jose Luis Sardina, Carmen Sanchez-Bernal, Jesus Sanchez-Yaguee, Benedicte Elena-Herrmann, Joran Villaret, Catherine Garrel, Julie Mondet, Pascal Mossuz, Angel Hernandez-Hernandez
Summary: Acute myeloid leukaemia (AML) is a highly heterogeneous disease, and the lack of NOX2 protein affects the metabolism control of AML cells. A panel of differentially expressed metabolic genes has been discovered, which has predictive value for AML prognosis and survival.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Edna Bechor, Anat Zahavi, Yevgeny Berdichevsky, Edgar Pick
Summary: This study demonstrates the important role of p67(phox) in the assembly/activation of NADPH oxidase through direct interaction with Nox2. Additionally, it shows that Rac-GTP acts as a carrier for p67(phox) to the membrane and induces a conformational change that enhances its affinity for Nox2, unmasking a previously hidden binding site.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Immunology
Chih-Fen Hu, San-Pin Wu, Gu-Jiun Lin, Chi-Chang Shieh, Chih-Sin Hsu, Jing-Wun Chen, Shih-Heng Chen, Jau-Shyong Hong, Shyi-Jou Chen
Summary: The study showed that Nox2 deficiency attenuates neural damage induced by EAE, reduces disease severity, pathogenic immune cells infiltration, demyelination, and oxidative stress in the CNS. It also revealed that microglial Nox2 plays a regulatory role in multiple pathways important for MS/EAE pathogenesis, suggesting that Nox2 inhibition may represent an important therapeutic target for MS.
FRONTIERS IN IMMUNOLOGY
(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
Multidisciplinary Sciences
Yuri M. Efremov, Daniel M. Suter, Peter S. Timashev, Arvind Raman
Summary: Recent developments in multi-harmonic Atomic Force Microscopy (AFM) techniques allow for fast and quantitative mapping of nanomechanical properties of living cells. This approach provides new insights into changes in subcellular mechanical properties due to disease or drug response. The proposed improvements in this study significantly enhance the resolution, identification, and quantification of sub-cellular and sub-nuclear structures using multi-harmonic AFM on living cells.
SCIENTIFIC REPORTS
(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, Medicinal
Igor A. Schepetkin, Gulmira Ozek, Temel Ozek, Liliya N. Kirpotina, Andrei Khlebnikov, Robyn A. Klein, Mark T. Quinn
Summary: This study isolated essential oils from five Artemisia species and found that these oils have immunosuppressive activity on human neutrophils, with the essential oils from A. dracunculus being the most effective. Further analysis identified farnesene as a potential anti-inflammatory modulator of human neutrophils.
Article
Biochemistry & Molecular Biology
Igor A. Schepetkin, Gulmira Ozek, Temel Ozek, Liliya N. Kirpotina, Andrei Khlebnikov, Mark T. Quinn
Summary: This study investigated the chemical composition and immunomodulatory activity of essential oils from Grindelia squarrosa. The main components of the oils were alpha-pinene, limonene, and borneol. The oils were found to activate human neutrophils and inhibit their responses to agonists.
Article
Biochemistry & Molecular Biology
Niccolo Cantini, Igor A. Schepetkin, Nadezhda V. Danilenko, Andrei I. Khlebnikov, Letizia Crocetti, Maria Paola Giovannoni, Liliya N. Kirpotina, Mark T. Quinn
Summary: Persistent inflammation contributes to various diseases. A study identified a range of compounds with anti-inflammatory activity, some of which act as FPR agonists while others inhibit inflammation through different signaling pathways. Further research is needed to define the molecular targets of these compounds and their relationship to FPR signaling.
Editorial Material
Chemistry, Multidisciplinary
Letizia Crocetti, Mark T. Quinn, Agostino Cilibrizzi, Maria Paola Giovannoni
FRONTIERS IN 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)
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
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)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)
