Article
Immunology
Xiaoting Liao, Weikang Zhang, Huijun Dai, Ren Jing, Mengling Ye, Wanyun Ge, Shenglin Pei, Linghui Pan
Summary: The study found that IL-17 plays a pro-inflammatory role in ventilator-induced lung injury (VILI) and could serve as a new target for treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Mahmoud Elshal, Marwa E. Abdelmageed
Summary: The study demonstrates that diacerein can prevent or reverse acetaminophen-induced hepatotoxicity in mice, indicating its potential clinical utility as a repurposed drug.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Mahmoud Elshal, Marwa E. Abdelmageed
Summary: The current study aimed to repurpose the anti-arthritic drug diacerein (DCN) for the treatment of acetaminophen-induced hepatotoxicity and investigate the underlying mechanisms. The results showed that DCN significantly reduced liver dysfunction, oxidative stress, hepatocyte necrosis, and inflammation, and inhibited acetaminophen-induced hepatocellular apoptosis. These effects were comparable to the existing treatment drug NAC.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Article
Immunology
Nayira A. Abdel Baky, Aya H. Al-Najjar, Hemat A. Elariny, Amany Said Sallam, Asmaa A. Mohammed
Summary: Pramipexole and lactoferrin have a protective effect against cyclophosphamide-induced hemorrhagic cystitis. Their mechanisms involve inhibiting oxidative stress, inflammation, and apoptosis, as well as modulating related signaling pathways.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Hematology
Ruth Shiloh, Ruth Lubin, Odeya David, Ifat Geron, Elimelech Okon, Idit Hazan, Marketa Zaliova, Gil Amarilyo, Yehudit Birger, Yael Borovitz, Dafna Brik, Arnon Broides, Sarit Cohen-Kedar, Liora Harel, Eyal Kristal, Daria Kozlova, Galina Ling, Mika Shapira Rootman, Noa Shefer Averbuch, Shiri Spielman, Jan Trka, Shai Izraeli, Simon Yona, Sarah Elitzur
Summary: In this study, the molecular pathway leading to histiocytosis and inflammation in H syndrome, a genetic disorder, was revealed through analysis of primary cells from patients. Loss of function of ENT3 was found to activate nucleoside-sensing toll-like receptors and downstream MAPK signaling, inducing cytokine secretion and inflammation. MEK inhibitor therapy showed effectiveness in resolving histiocytosis and inflammation in a patient with H syndrome.
Article
Immunology
Sara Francisco, Alicia Arranz, Javier Merino, Carmen Punzon, Rosario Perona, Manuel Fresno
Summary: The study found that TLR2 ligands activate MAPKs p38 and ERK earlier in macrophages, leading to higher levels of IL-10/IL-12 and IL-10/TNF-alpha ratios compared to TLR4 ligand LPS. Early TLR2-mediated p38 induction contributes to high IL-10 production, likely suppressing host Th1 response against certain pathogens.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Satomi Miki, Jun-ichiro Suzuki, Miyuki Takashima, Mari Ishida, Hiroki Kokubo, Masao Yoshizumi
Summary: Overall, our study demonstrates that S1PC, a sulfur compound found in AGE, can enhance anti-inflammatory effects and promote M2c macrophage polarization, thus showing potential in improving atherosclerosis.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Lindsay M. Snyder, Claire M. Doherty, Heather L. Mercer, Eric Y. Denkers
Summary: Our study identified MyD88-independent intestinal immune pathways induced by T. gondii, including myeloid cell-derived IL-12 production, downstream type I immunity, and IFN-gamma production by ILC1, ILC3, and T lymphocytes. This reveals an underlying network of immune responses that do not involve signaling through MyD88.
Article
Multidisciplinary Sciences
Jianjie Zhou, Yu Xiao, Yifei Ren, Jiwan Ge, Xinquan Wang
Summary: The TIR domains in the IL-1R family play a crucial role in signal transmission, and the structurally variant regions and key residues in the helices greatly impact the signaling process.
Article
Multidisciplinary Sciences
Wojciech Dawicki, Hui Huang, Yanna Ma, Jennifer Town, Xiaobei Zhang, Chris D. Rudulier, John R. Gordon
Summary: CD40 signaling in DC10 plays a crucial role in promoting IL-10 expression and robust induction of tolerance, including activation of induced Treg.
Article
Anatomy & Morphology
Jie Wei, Guopeng You, Hongjuan Cheng, Chen Gao
Summary: This study investigated the role of SPRED2 in the development of osteoarthritis (OA). It was found that SPRED2 promoted autophagy and attenuated inflammatory response in IL-1 beta-induced OA chondrocytes by regulating the p38 MAPK signaling pathway. SPRED2 was downregulated in human knee cartilage tissues of OA patients and in IL-1 beta-induced chondrocytes.
Article
Biochemistry & Molecular Biology
Nadeem Akhter, Ajit Wilson, Reeby Thomas, Fatema Al-Rashed, Shihab Kochumon, Areej Al-Roub, Hossein Arefanian, Ashraf Al-Madhoun, Fahd Al-Mulla, Rasheed Ahmad, Sardar Sindhu
Summary: IL-8/MCP-1 expression in adipose tissue is elevated in obesity. The synergistic effect of ROS/TNF-alpha can drive the expression of chemokines in monocytic cells, potentially through inducing ER stress, HIF1A stabilization, and signaling via NF-kappa B/ERK-1,2. NAC may have a therapeutic significance in inhibiting oxidative stress-driven IL-8/MCP-1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Integrative & Complementary Medicine
Li Teng, Yue Shen, Yuhan Qu, Longfei Yang, Yuting Yang, Xi Jian, Shengli Fan, Lele Zhang, Qiang Fu
Summary: This study investigated the potential anti-osteoarthritis activity of cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan. In vitro experiments showed that cyasterone effectively inhibited chondrocyte apoptosis, promoted the expression of collagen II and aggrecan, and suppressed the production of inflammatory factors induced by interleukin (IL)-1/I. In vivo experiments demonstrated that cyasterone alleviated the inflammatory response and cartilage destruction in a rat model of osteoarthritis.
CHINESE JOURNAL OF NATURAL MEDICINES
(2023)
Review
Cell Biology
Clovis H. T. Seumen, Tanja M. Grimm, Christof R. Hauck
Summary: Toll-like receptors (TLRs) play a crucial role in immune response, but exaggerated activation can lead to inflammatory diseases. This review discusses the impact of protein phosphorylation on TLR signaling, highlighting the role of phosphatases as negative regulators. Understanding phosphatase-mediated regulation could offer new approaches to modulate immune signaling.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Biochemistry & Molecular Biology
Tsvetana Petrova, Jiazhen Zhang, Sambit K. Nanda, Clara Figueras-Vadillo, Philip Cohen
Summary: The atypical E3 ligase HOIL-1 plays a role in restricting IL-18 signaling and cytokine production by forming ester-linked ubiquitin bonds, with implications for immune cell activation. Changes in HOIL-1-catalysed ester-linked ubiquitylation can promote or reduce cytokine production depending on the context, potentially due to differences in the ubiquitylation of IRAK2.
Article
Multidisciplinary Sciences
Tsvetana Petrova, Jelena Pesic, Katerina Pardali, Matthias Gaestel, J. Simon C. Arthur
SCIENTIFIC REPORTS
(2020)
Editorial Material
Immunology
Henry J. McSorley, J. Simon C. Arthur
MUCOSAL IMMUNOLOGY
(2020)
Article
Neurosciences
Oladiran I. Olateju, Lorenzo More, J. Simon C. Arthur, Bruno G. Frenguelli
Summary: Neurogenesis in the adult hippocampus can be stimulated by exposure to an enriched environment, leading to increased production of neurons and benefits for health and cognition. MSK1 plays a negative regulatory role post-enrichment by influencing the number of cells destined to become neurons, thereby potentially serving as a homeostatic control on the integration of new neurons into the dentate gyrus.
Article
Biochemistry & Molecular Biology
Nicola J. Darling, J. Simon C. Arthur, Philip Cohen
Summary: The study demonstrates the essential roles of salt-inducible kinases (SIKs) in producing inflammatory mediators in response to IL-33 stimulation, which play a critical role in regulating airway inflammation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Judit Remenyi, Rangeetha Jayaprakash Naik, Jinhua Wang, Momchil Razsolkov, Alyssa Verano, Quan Cai, Li Tan, Rachel Toth, Samantha Raggett, Carla Baillie, Ryan Traynor, C. James Hastie, Nathanael S. Gray, J. Simon C. Arthur
Summary: JAK3 has been proposed as an ideal drug target for immune disorders due to its restricted expression in the immune system and requirement for cytokine signaling. Mutating the cysteine residue to serine in JAK3 increases the IC50 for covalent inhibitors. Mice with the Cys905Ser mutation in the JAK3 gene provide a chemical-genetic model to study JAK3 function.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Naveed Akbar, Calum Forteath, Muhammad S. Hussain, Kathleen Reyskens, Jill J. F. Belch, Chim C. Lang, Ify Mordi, U. Bhalraam, J. Simon C. Arthur, Faisel Khan
Summary: In this study, it was found that mitogen and stress kinase 1/2 (MSK1/2) play a significant role in the development of endothelial dysfunction in myocardial infarction patients and mouse models. Genetic deficiency of MSK1/2 increased plasma levels of pro-inflammatory cytokines and promoted endothelial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Meriam Nefla, Nicola J. Darling, Manuel van Gijsel Bonnello, Philip Cohen, J. Simon C. Arthur
Summary: Salt Inducible Kinases 2 (SIK2) and 3 (SIK3) play important roles in thymic T cell development, with their loss leading to decreased numbers of peripheral T cells and defects in negative and/or positive selection in the thymus.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Emma L. Robinson, Faye M. Drawnel, Saher Mehdi, Caroline R. Archer, Wei Liu, Hanneke Okkenhaug, Kanar Alkass, Jan Magnus Aronsen, Chandan K. Nagaraju, Ivar Sjaastad, Karin R. Sipido, Olaf Bergmann, J. Simon C. Arthur, Xin Wang, H. Llewelyn Roderick
Summary: This study demonstrates the importance of MAPK pathways in regulating gene expression during cardiac hypertrophy and provides mechanistic insights into the coupling of MAPK stimulation and IEG induction through MSK-mediated phosphorylation of histone H3, which recruits Brg1 to initiate gene expression.
Article
Multidisciplinary Sciences
Dylan G. Ryan, Elena Knatko, Alva M. Casey, Jens L. Hukelmann, Sharadha Dayalan Naidu, Alejandro J. Brenes, Thanapon Ekkunagul, Christa Baker, Maureen Higgins, Laura Tronci, Efterpi Nikitopolou, Tadashi Honda, Richard C. Hartley, Luke A. J. O'Neill, Christian Frezza, Angus Lamond, Andrey Y. Abramov, J. Simon C. Arthur, Doreen A. Cantrell, Michael P. Murphy, Albena T. Dinkova-Kostova
Summary: Cells have evolved cytoprotective protein networks controlled by Nrf2 and Keap1 to overcome oxidative, inflammatory, and metabolic stress. Activation of Nrf2 facilitates metabolic reprogramming and mitochondrial adaptation, and fine-tunes the innate immune response in macrophages.
Article
Biochemistry & Molecular Biology
Manuel van Gijsel-Bonnello, Nicola J. Darling, Takashi Tanaka, Samuele Di Carmine, Francesco Marchesi, Sarah Thomson, Kristopher Clark, Mariola Kurowska-Stolarska, Henry J. McSorley, Philip Cohen, J. Simon C. Arthur
Summary: The study shows that nintedanib, a tyrosine kinase inhibitor used for treating idiopathic pulmonary fibrosis, also inhibits salt-inducible kinase 2, which may contribute to its effectiveness in treating lung fibrosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Lorenzo More, Lucia Privitera, Philippa Perrett, Daniel D. Cooper, Manuel Van Gijsel Bonnello, J. Simon C. Arthur, Bruno G. Frenguelli
Summary: The transcription factor CREB plays a crucial role in regulating physiological functions in the central nervous system. Recent research has focused on the phosphorylation of the S133 residue in CREB, which is required for its transcriptional activation. Previous studies using molecular genetic techniques have resulted in conflicting results, possibly due to the manipulation of endogenous CREB. In this study, the researchers generated a postnatal and forebrain-specific mutant of CREB S133A to avoid potential complications. The findings show that CREB S133 is necessary for spatial cognitive flexibility, basal synaptic transmission, and long-term potentiation in the hippocampus, highlighting its importance in neuronal function, synaptic plasticity, and cognition.
Article
Biochemistry & Molecular Biology
Laura Boccuni, Elke Podgorschek, Moritz Schmiedeberg, Ekaterini Platanitis, Peter Traxler, Philipp Fischer, Alessia Schirripa, Philipp Novoszel, Angel R. Nebreda, J. Simon C. Arthur, Nikolaus Fortelny, Matthias Farlik, Veronika Sexl, Christoph Bock, Maria Sibilia, Pavel Kovarik, Mathias Mueller, Thomas Decker
Summary: This study reveals the synergistic effect of cell stress-induced p38 MAPK signaling and IFN-stimulated signal transduction, and the impact of this synergy on ISG expression and macrophage infection ability.
Review
Cardiac & Cardiovascular Systems
Zhen Hui Peh, Adel Dihoum, Dana Hutton, J. Simon C. Arthur, Graham Rena, Faisel Khan, Chim C. C. Lang, Ify R. Mordi
Summary: HFpEF is a type of heart failure that accounts for around half of all cases and may become the dominant type in the future. Compared to heart failure with reduced ejection fraction, there are limited evidence-based treatment strategies available for HFpEF. Inflammation is believed to play a key role in the pathophysiology of HFpEF and could be a potential therapeutic target.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cell Biology
Lorenzo More, Lucia Privitera, Daniel D. Cooper, Marianthi Tsogka, J. Simon C. Arthur, Bruno G. Frenguelli
Summary: Positive experiences, such as social interaction, cognitive training, and physical exercise, can improve cognitive abilities and synaptic plasticity associated with ageing. However, the mechanisms through which the environment influences neuronal response and adaptation to these positive sensory experiences remain unclear.
Article
Biochemical Research Methods
Christa P. Baker, Iain R. Phair, Alejandro J. Brenes, Abdelmadjid Atrih, Dylan G. Ryan, Roland Bruderer, Albena T. Dinkova-Kostova, Douglas J. Lamont, J. Simon C. Arthur, Andrew J. M. Howden
Summary: Here, an optimized protocol for analyzing murine bone-marrow-derived macrophages using label-free data-independent acquisition (DIA) proteomics is described. The protocol includes sample preparation utilizing the S-Trap method, mass spectrometry data acquisition, and data analysis approaches. The single-shot DIA protocol achieves comparable proteomic depth with data-dependent MS approaches, making it suitable for large sample numbers with high experimental reproducibility.
