Article
Clinical Neurology
Anan Shtaya, Leslie R. Bridges, Rebecca Williams, Sarah Trippier, Liqun Zhang, Anthony C. Pereira, James A. R. Nicoll, Delphine Boche, Atticus H. Hainsworth
Summary: The study identified an anti-inflammatory process occurring alongside neuroinflammation post-sICH in clinical patients, involving native microglia and blood monocytes. This novel pathway offers therapeutic targets and a treatment opportunity window for delivering therapeutics through invading monocytes during 3-5 days post-sICH.
Article
Cell Biology
Joseph Hiatt, Devin A. Cavero, Michael J. McGregor, Weihao Zheng, Jonathan M. Budzik, Theodore L. Roth, Kelsey M. Haas, David Wu, Ujjwal Rathore, Anke Meyer-Franke, Mohamed S. Bouzidi, Eric Shifrut, Youjin Lee, Vigneshwari Easwar Kumar, Eric Dang, David E. Gordon, Jason A. Wojcechowskyj, Judd F. Hultquist, Krystal A. Fontaine, Satish K. Pillai, Jeffery S. Cox, Joel D. Ernst, Nevan J. Krogan, Alexander Marson
Summary: A method for delivering CRISPR-Cas9 ribonucleoprotein complexes via nucleofection into human monocytes has been developed for precise gene knockout and differentiation into macrophages or dendritic cells. This system shows promise for genetic studies of human myeloid cells in various areas such as immune signaling, inflammation, cancer immunology, host-pathogen interactions, and beyond.
Article
Cell Biology
Atif Zafar, Hang Pong Ng, E. Ricky Chan, Sally L. Dunwoodie, Ganapati H. Mahabeleshwar
Summary: In this study, it was found that CITED2 is an essential negative regulator of pro-inflammatory macrophage activation and inflammatory disease pathogenesis. Myeloid-CITED2 deficiency significantly elevates HFD-induced expansion of adipose tissue volume, obesity, glucose intolerance, and insulin resistance. CITED2 promotes BCL6 expression by restraining STAT5 activation in macrophages, thereby limiting inflammation, preventing obesity, and insulin resistance.
Article
Immunology
Nadeem Akhter, Shihab Kochumon, Amal Hasan, Ajit Wilson, Rasheeba Nizam, Ashraf Al Madhoun, Fatema Al-Rashed, Hossein Arefanian, Fawaz Alzaid, Sardar Sindhu, Fahd Al-Mulla, Rasheed Ahmad
Summary: The co-stimulation of IFN-gamma and LPS can enhance the expression of CCL2 through the acetylation of H3K27, leading to augmented inflammation in obesity. These findings contribute to a better understanding of the regulatory mechanisms of CCL2 in the pathogenesis of obesity.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Physiology
Byeong J. Chun, Surya P. Aryal, Peter Varughese, Bin Sun, Joshua A. Bruno, Chris I. Richards, Adam D. Bachstetter, Peter M. Kekenes-Huskey
Summary: ATP and its metabolites activate purinergic receptors to drive microglia migration and cytokine production. Our computational model provides insights into how different characteristics of calcium waveforms influence microglial function. We also identify CD39 metabolism as a regulator of purinergic receptor-induced calcium responses, and predict calcium transients and cell membrane displacements in a BV2 microglia cell line.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Katrin Richter, Veronika Grau
Summary: Nicotinic acetylcholine receptors are expressed in not only the nervous system and neuro-muscular junction, but also in mononuclear phagocytes of the innate immune system. These cells, which include monocytes, macrophages, and dendritic cells, play important roles in host defense and inflammatory diseases. The stimulation of nicotinic acetylcholine receptors in these cells is associated with anti-inflammatory effects. However, the underlying molecular mechanisms are still not fully understood.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Endocrinology & Metabolism
Esther Dos Santos, Hadia Moindjie, Valerie Serazin, Lucie Arnould, Yoann Rodriguez, Khadija Fathallah, Eytan R. Barnea, Francois Vialard, Marie-Noelle Dieudonne
Summary: The study demonstrates that PIF can enhance decidualization and limit trophoblast invasion by increasing the production of endometrial factors. PIF appears to be a pivotal player in the human embryo implantation process by controlling both trophoblast and endometrial cells.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
D. Wu, Y. Weng, Y. Feng, B. Liang, H. Wang, L. Li, Z. Wang
Summary: In periodontitis, Trem1 regulates polarization of M1 macrophages through the STAT3/HIF-1α signaling pathway. Studies suggest that targeting Trem1 could be a potential strategy for the treatment of periodontitis by modulating macrophage polarization.
JOURNAL OF DENTAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Emelie Barreby, Benedikt Strunz, Sebastian Nock, Lea Naudet, Joanne X. Shen, Helene Johansson, Isabella Soennerborg, Junjie Ma, Egon Urgard, Laura J. Pallett, Yizhou Hu, Achilleas Fardellas, Valerio Azzimato, Ana Vankova, Laura Levi, Cecilia Morgantini, Mala K. Maini, Per Stal, Stephan P. Rosshart, Jonathan M. Coquet, Greg Nowak, Erik Naeslund, Volker M. Lauschke, Ewa Ellis, Niklas K. Bjoerkstroem, Ping Chen, Myriam Aouadi
Summary: By studying patients undergoing liver transplantation, a specific population of resident liver myeloid cells that protects against metabolic impairment in obesity is identified. These cells, termed liver myeloid cells 2 (LM2), decrease in proportion during obesity but can ameliorate oxidative stress. These findings suggest that targeting resident myeloid cells could be a therapeutic approach for reducing oxidative stress in non-alcoholic fatty liver disease (NAFLD).
Article
Medicine, Research & Experimental
P. Vishnyakova, A. Poltavets, E. Karpulevich, A. Maznina, V. Vtorushina, L. Mikhaleva, E. Kananykhina, A. Lokhonina, S. Kovalchuk, A. Makarov, A. Elchaninov, G. Sukhikh, T. Fatkhudinov
Summary: Macrophages play a crucial role in innate immunity and are activated by various factors. This study found that macrophages derived from CD14+ monocytes exhibit higher sensitivity to pro-inflammatory induction, showing increased levels of pro-inflammatory and anti-inflammatory cytokines compared to CD16+-derived macrophages. This data may be valuable for macrophage-based cell therapy applications, providing insights for manipulating donor monocytes for transplantation.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Immunology
Buesra Geckin, Gizem Kilic, Priya A. Debisarun, Konstantin Fohse, Azahara Rodriguez-Luna, Pablo Fernandez-Gonzalez, Ana Lopez Sanchez, Jorge Dominguez-Andres
Summary: The proper functioning of the immune system relies on the balance between pro-inflammation and anti-inflammation. Disruption of this balance can lead to autoimmune or inflammatory diseases. A fungal compound called AM3 has been found to modulate immune responses by decreasing excessive cytokine production and maintaining the capacity of immune cells to respond to stimuli. AM3 may help reduce immune activation and keep immune responses within a normal range.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dan Mao, Hiroshi Inoue, Takuya Notomi, Seiji Goda
Summary: The p38a isoform is crucial for TNF-a-induced IL-8 production in Ca9-22 cells, and its activation is associated with the phosphorylation of threonine 180 and tyrosine 182. This study highlights p38a as a potential therapeutic target for preventing and treating periodontal disease.
Article
Multidisciplinary Sciences
Swee Heng Milon Pang, Joshua D'Rozario, Senora Mendonca, Tejasvini Bhuvan, Natalie L. Payne, Di Zheng, Assifa Hisana, Georgia Wallis, Adele Barugahare, David Powell, Jai Rautela, Nicholas D. Huntington, Grant Dewson, David C. S. Huang, Daniel H. D. Gray, Tracy S. P. Heng
Summary: Multipotent mesenchymal stromal cells (MSCs) have therapeutic benefits in preclinical models, with their apoptosis and immunosuppressive effects playing a crucial role in reducing disease severity and highlighting implications for cell-based therapies.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Daniel Tortolani, Camilla Di Meo, Sara Standoli, Francesca Ciaramellano, Salam Kadhim, Eric Hsu, Cinzia Rapino, Mauro Maccarrone
Summary: Rare cannabis-derived phytocannabinoids (pCBs) have therapeutic potential in skin disorders and their anti-inflammatory effects were investigated in this study. The experiment involved using lipopolysaccharide (LPS) to induce inflammation in human keratinocytes (HaCaT cells) and measuring the levels of pro-inflammatory interleukins. The results showed that pCBs significantly reduced the release of pro-inflammatory interleukins and modulated MAPK signaling, suggesting their potential as a treatment for inflammation-related skin pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Guoshuai Feng, Geetika Bajpai, Pan Ma, Andrew Koenig, Andrea Bredemeyer, Inessa Lokshina, Lulu Lai, Irmgard Foerster, Florian Leuschner, Daniel Kreisel, Kory J. Lavine
Summary: This study identified CCL17 as a proinflammatory mediator in CCR2(+) macrophages and dendritic cells, and suggested that inhibiting CCL17 could promote Treg recruitment and suppress myocardial inflammation.
Article
Critical Care Medicine
Michael C. McKelvey, Anthony A. Abladey, Donna M. Small, Declan F. Doherty, Richard Williams, Aaron Scott, C. Arnold Spek, Keren S. Borensztajn, Leslie Holsinger, Robert Booth, Cecilia M. O'Kane, Daniel F. McAuley, Clifford C. Taggart, Sinead Weldon
Summary: This study investigates the role of cathepsin S in acute respiratory distress syndrome (ARDS), a condition without specific pharmacological treatments. The results show that cathepsin S contributes to acute lung injury and could be a potential therapeutic target for ARDS. The study demonstrates that elevated cathepsin S activity and concentration are associated with acute lung inflammation, leading to neutrophil recruitment and protein leakage. Additionally, the study suggests that cathepsin S mediates its pathogenic effects partly through protease-activated receptor-1.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Critical Care Medicine
Philip Toner, Andrew J. Boyle, James J. McNamee, Kathryn Callaghan, Christopher Nutt, Paul Johnston, John Trinder, Margaret McFarland, Rejina Verghis, Daniel F. McAuley, Cecilia M. O'Kane
Summary: This study aimed to investigate the safety and efficacy of enteral aspirin in adult patients with ARDS. However, the trial was stopped early due to slow recruitment. The results showed that aspirin did not significantly improve the oxygenation index or other physiological outcomes. There was also no difference in the number of adverse events between the groups.
Review
Biochemistry & Molecular Biology
Flavia Viana, Cecilia M. O'Kane, Gunnar N. Schroeder
Summary: Research on the mechanisms of respiratory infections is often limited by the current models used. Precision-cut lung slices (PCLS) offer a promising ex vivo organotypic model that retains the cellular complexity and architecture of the lung, providing a platform for investigating respiratory pathogens in a near-native environment.
MOLECULAR MICROBIOLOGY
(2022)
Article
Chemistry, Analytical
Alice H. Iles, Peijun J. W. He, Ioannis N. Katis, Panagiotis P. Galanis, Anto J. U. K. John, Paul Elkington, Robert W. Eason, Collin L. Sones
Summary: Inflammatory markers CRP and PCT are useful in improving triage speed and preventing inappropriate antibiotic use. A novel multiplexed LFD can rapidly and semi-quantitatively detect CRP and PCT, showing potential for rapid treatment of patients with suspected pneumonia.
Review
Respiratory System
Tommaso Morelli, Kohei Fujita, Gil Redelman-Sidi, Paul T. Elkington
Summary: Immune checkpoint inhibitors (ICIs) have greatly impacted cancer treatment, but immune-related adverse events (irAEs) and infections caused by immunosuppression are common issues. However, some infections can be triggered by ICIs without immunosuppressive treatment, characterized by dysregulated immune responses. A new framework is needed to consider such infections in the context of cancer immunotherapy.
Review
Biochemistry & Molecular Biology
Paul Elkington, Marta E. Polak, Michaela T. Reichmann, Alasdair Leslie
Summary: Mycobacterium tuberculosis is the main pathogen causing tuberculosis and poses a serious threat to human health. Understanding its pathogenic mechanisms is crucial for effectively combating this pathogen. Recent studies have found that extracellular matrix (ECM) remodeling plays an important role in the development of the disease.
TRENDS IN MOLECULAR MEDICINE
(2022)
Article
Oncology
Kohei Fujita, Paul Elkington, Gil Redelman-Sidi, Osamu Kanai, Yuki Yamamoto, Takuma Imakita, Misato Okamura, Koichi Nakatani, Tadashi Mio
Summary: This study evaluated the conversion rate of interferon-gamma release assay (IGRA) and the incidence of active tuberculosis during immunotherapy, finding that some patients developed IGRA conversion and active tuberculosis during ICI therapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Review
Respiratory System
Mohamed Ahmed, Liku B. Tezera, Paul T. Elkington, Alasdair J. Leslie
Summary: Immune checkpoints play a crucial role in regulating T-cell activation and can limit anti-tumour responses. However, boosting T-cell immunity by blocking the PD-1/PD-L1 axis can trigger reactivation of latent tuberculosis. Inhibitory receptors are important for maintaining immune function and preventing excessive tissue damage.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Immunology
N. F. Walker, F. Karim, M. Y. S. Moosa, S. Moodley, M. Mazibuko, K. Khan, T. R. Sterling, Y. F. van der Heijden, A. D. Grant, P. T. Elkington, A. Pym, A. Leslie
Summary: Current methods for tuberculosis treatment monitoring are not optimal. This study evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations as potential biomarkers for tuberculosis treatment monitoring. The results showed that plasma concentrations of MMP-1, MMP-8, and MMP-10 decreased significantly during treatment, while plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive participants, both before and after 6 months of treatment. Therefore, plasma MMP-8 has the potential to enhance tuberculosis treatment monitoring and screen for culture positivity.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Editorial Material
Critical Care Medicine
Kenneth G. Castro, Lucica Ditiu, Suvanand Sahu, Francine Ntoumi, Simon Tiberi, Cecilia M. O'Kane, Onno Akkerman, Katerina Manika, Peter Mwaba, Lina Davies Forsman, Eskild Petersen, Eleni Aklillu, Esam Azhar, Daniela M. Cirillo, Giovanni-Battista Migliori, Aula Abbara, Alimuddin Zumla
LANCET RESPIRATORY MEDICINE
(2022)
Article
Respiratory System
Maria Victoria Humbert, Cosma Mirella Spalluto, Joseph Bell, Cornelia Blume, Franco Conforti, Elizabeth R. Davies, Lareb S. N. Dean, Paul Elkington, Hans Michael Haitchi, Claire Jackson, Mark G. Jones, Matthew Loxham, Jane S. Lucas, Hywel Morgan, Marta Polak, Karl J. Staples, Emily J. Swindle, Liku Tezera, Alastair Watson, Tom M. A. Wilkinson
Summary: Respiratory diseases are a significant burden to healthcare systems globally, and the differences in mouse models hinder the translation of research findings to the clinic. Therefore, it is crucial to develop models that accurately recreate the complexity of the human lung. Advances in micro-engineering and tissue engineering have enabled the development of more sophisticated models aiming to bridge the gap between native lungs and in vitro replicates.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Infectious Diseases
Ximena Gonzalo, Magdalena K. Bielecka, Liku Tezera, Paul Elkington, Francis Drobniewski
Summary: In this study, a novel physiological 3-D bioelectrospray model of tuberculosis granuloma was used to evaluate the activity of different drugs. The results showed that clofazimine was the most effective drug, while carbapenems and nitazoxanide had less activity against Mycobacterium tuberculosis.
Article
Biology
Mohamed Ahmed, Jared Mackenzie, Liku Tezera, Robert Krause, Barry Truebody, Diana Garay-Baquero, Andres Vallejo, Katya Govender, John Adamson, Hayden Fisher, Jonathan W. Essex, Salah Mansour, Paul Elkington, Adrie J. C. Steyn, Alasdair Leslie
Summary: Studies have shown that Interferon-gamma (IFN-gamma) has a direct effect on the oxygen consumption rate and respiration of Mycobacterium tuberculosis (Mtb), different from other cytokines. Mass spectrometry and molecular modeling studies have revealed that IFN-gamma interacts with mycobacterial membrane protein large 10 (MmpL10). Furthermore, IFN-gamma promotes Mtb growth and eliminates drug-resistant strains.
COMMUNICATIONS BIOLOGY
(2022)
Letter
Critical Care Medicine
Philip Toner, Daniel F. McAuley, Cecilia M. O'Kane
Article
Critical Care Medicine
Andrew James Boyle, Peter Ferris, Ian Bradbury, John Conlon, Manu Shankar-Hari, Angela J. Rogers, Cecilia M. O'Kane, Daniel F. McAuley
Summary: Patients with high baseline plasma IL-18 in ARDS have increased mortality rates, but simvastatin can reduce this risk and improve survival by reducing inflammasome activation.