Article
Microbiology
Axel Dietschmann, Sebastian Schruefer, Stefanie Westermann, Fiona Henkel, Kirstin Castiglione, Ralf Willebrand, Jasmin Adam, Jurgen Ruland, Roland Lang, Donald C. Sheppard, Julia Esser-von-Bieren, Daniel Radtke, Sven Krappmann, David Voehringer
Summary: Eosinophilia is associated with various inflammatory diseases, such as allergic bronchopulmonary aspergillosis (ABPA). It has been shown that direct interaction between eosinophils and Aspergillus fumigatus is essential for the activation of eosinophils, which then secrete multiple proinflammatory mediators. The PI3K-AKT-mTOR pathway plays a crucial role in A. fumigatus-induced eosinophil activation.
Review
Biotechnology & Applied Microbiology
Jan Dohnalek, Tereza Skalova
Summary: The C-type lectin-like fold (CTL fold) is a versatile structural motif found in many proteins, and its interactions play significant roles in various biological processes. Understanding the rules governing these interactions can aid in the development of new protein binders for biomedical and biotechnological applications.
BIOTECHNOLOGY ADVANCES
(2022)
Article
Multidisciplinary Sciences
Jonathan L. Gillan, Mithil Chokshi, Gareth R. Hardisty, Sara Clohisey Hendry, Daniel Prasca-Chamorro, Nicola J. Robinson, Benjamin Lasota, Richard Clark, Lee Murphy, Moira K. B. Whyte, J. Kenneth Baillie, Donald J. Davidson, Gang Bao, Robert D. Gray
Summary: An intense and nonresolving airway inflammatory response in cystic fibrosis (CF) leads to destructive lung disease. Dysregulation of macrophage immune function may play a key role in the progression of CF lung disease. Transcriptome sequencing revealed significantly distinct transcriptional programs in CF and non-CF macrophages, including a blunted type I interferon signaling response in CF macrophages. However, this immune defect can be reversed by treatment with CFTR modulators or gene editing.
Article
Immunology
Huanghui Wu, Han Bao, Cong Liu, Qiao Zhang, Ailing Huang, Minxue Quan, Chunhui Li, Ying Xiong, Guozhong Chen, Lichao Hou
Summary: This study investigated the role and mechanism of extracellular nucleosomes and histones, as damage-associated molecular patterns (DAMPs), in progressive neuroinflammation and chronic stress-related emotional disorders. It found that extracellular nucleosomes accelerate microglial inflammation via Clec2d and TLR9, contributing to chronic stress-induced emotional disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Xin Zhang, Jia-Rui Yuan, Xin Wang, Shuang Fu, Rui-Tao Wang, Guang-Yu Wang
Summary: This study investigates the association between plasma CLEC-2 levels and microsatellite status in CRC patients. The results demonstrate that CLEC-2 levels are significantly higher in patients with high microsatellite instability phenotype.
Review
Immunology
Michal Scur, Brendon D. Parsons, Sayanti Dey, Andrew P. Makrigiannis
Summary: Our understanding of CTLRs has expanded beyond their initial roles in pathogen recognition, now encompassing scavenger receptor activity, cell death and cell transformation sensing, and immune response regulation. The diversity in expression and signaling activity among individual CTLR members, as well as the discovery of new receptor binding capabilities and interactions, cellular expression profiles, and receptor structures and signaling mechanisms, has revealed the defining roles of CTLRs in immunity. NK cell receptors, specifically the NKRP1 family of CTLRs, exemplify this functional diversity, displaying essential immune functions beyond NK cells. It is crucial to better understand the functional potential of these receptor families in immune defense and pathology, given the ever-expanding evidence for their involvement in various biological processes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Shojiro Haji, Taiki Ito, Carla Guenther, Miyako Nakano, Takashi Shimizu, Daiki Mori, Yasunori Chiba, Masato Tanaka, Sushil K. Mishra, Janet A. Willment, Gordon D. Brown, Masamichi Nagae, Sho Yamasaki
Summary: This study reports that human Dectin-1 acts as a ligand for CLEC-2 and highlights the importance of glycosylation in its function as a CLEC-2 ligand. Furthermore, it is shown that expression of human Dectin-1 can rescue the lethality and lymphatic defect resulting from a deficiency of Podoplanin.
Article
Oncology
Meng-Lin Zhang, Wen-Juan Huang, Chen-Xi Yue, Ming-Ming Li, Na Li, Rui-Tao Wang, Rui Xie
Summary: This study found that CRC patients have higher levels of CLEC-2 compared to patients with colorectal polyps, with significant differences in CLEC-2 levels among different polyp subtypes. CLEC-2 shows potential clinical value for screening CRC and differentiating colorectal polyps from CRC.
Article
Immunology
Kazuya Tone, Mark H. T. Stappers, Remi Hatinguais, Ivy M. Dambuza, Fabian Salazar, Carol Wallace, Raif Yuecel, Petruta L. Morvay, Kazuyoshi Kuwano, Janet A. Willment, Gordon D. Brown
Summary: Environmental fungal component melanin, recognized by a novel C-type lectin receptor MelLec, is shown to promote pulmonary allergic inflammation and Th17 T-cells development in response to Aspergillus fumigatus spores. Surprisingly, MelLec deficiency was protective with reduced pulmonary inflammation, while maintaining increased fungal burdens, suggesting a complex role of MelLec in controlling pulmonary fungal burden while impacting inflammatory responses negatively in this allergic model.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Tianhang Li, Tianyao Liu, Zihan Zhao, Yuchen Pan, Xinyan Xu, Yulin Zhang, Shoubin Zhan, Shengkai Zhou, Wenjie Zhu, Hongqian Guo, Rong Yang
Summary: Immunotherapies offer new treatment options for urothelial bladder cancer, but their efficacy is limited by heterogeneity and therapeutic resistance. Research has shown that the commensal microbiota and its interactions with host immunity play a crucial role in bladder cancer. The urinary mycobiome and C-type lectin receptors (CLRs) may be potential targets for immunotherapy in bladder cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Apparao B. Kummarapurugu, Shuo Zheng, Abigail Pulsipher, Justin R. Savage, Jonathan Ma, Bruce K. Rubin, Thomas P. Kennedy, Judith A. Voynow
Summary: In this study, the synthetic compound GM-1111 showed effective anti-NE activity in CF sputum, facilitating DNA depolymerization and reducing sputum elasticity. These findings suggest that GM-1111 could be a promising therapeutic option for CF patients, with potential advantages over traditional unfractionated heparin.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Review
Infectious Diseases
Lauren C. Magee, Mariam Louis, Vaneeza Khan, Lavender Micalo, Nauman Chaudary
Summary: Cystic Fibrosis is a genetic disease caused by a mutation in the CFTR protein, leading to respiratory issues. CF patients are often colonized or infected with fungi, but diagnosing and treating fungal colonization and active infections in adult CF patients remains challenging. Limited data is available for eradication and treatment.
INFECTION AND DRUG RESISTANCE
(2021)
Article
Hematology
Zhaogong Zhi, Natalie J. Jooss, Yi Sun, Martina Colicchia, Alexandre Slater, Luis A. Moran, Hilaire Yam Fung Cheung, Ying Di, Julie Rayes, Natalie S. Poulter, Steve P. Watson, Asif J. Iqbal
Summary: In this study, Gal-9 was identified as a novel platelet agonist that induces activation through interaction with GPVI and CLEC-2.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Infectious Diseases
Margherita Degasperi, Riccardo Sgarra, Mario Mardirossian, Sabrina Pacor, Massimo Maschio, Marco Scocchi
Summary: This study developed a prodrug to extend the peptide chain of an antimicrobial peptide and added a sequence that can activate the peptide at the site of infection/inflammation, enabling a slow and targeted release. The prodrug showed good antimicrobial activity and lower cytotoxicity in the presence of elastase.
Article
Biochemistry & Molecular Biology
Jia Peng, Jiacheng Li, Jingjie Liang, Wanbo Li, Yao Yang, Yukai Yang, Sen Zhang, Xiaolin Huang, Fang Han
Summary: A C-type lectin-like receptor cluster of differentiation CD302 (YdCD302) in yellow drum was found to be involved in disease resistance against Vibrio harveyi infection. YdCD302 showed high expression in liver and exhibited agglutination and antibacterial activity against V. harveyi cells. The interaction between YdCD302 and V. harveyi cells activated reactive oxygen species production and induced cell death. Up-regulation of YdCD302 expression in immune organs after V. harveyi infection suggests its involvement in innate immunity. This study provides insights into the genetic basis and functional role of YdCD302 in disease resistance.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Editorial Material
Respiratory System
Julian T. Forton
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Respiratory System
Rebecca Weiser, Juliette Oakley, Katherine Ronchetti, Jo-Dee Tame, Sven Hoehn, Tomasz P. Jurkowski, Eshwar Mahenthiralingam, Julian T. Forton
Summary: Spatial heterogeneity of the lower airway microbiota was observed in children with cystic fibrosis (CF). Induced sputum (IS) sampling was found to capture a representative microbiota signature of the lower airway in CF children.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Veterinary Sciences
Magdalena A. Czubala, Eva Eilles, Andreas Staubi, Natacha Ipseiz, Michael Vogt, Leonie Zieglowski, Lisa Ernst, Rene H. Tolba, Philip R. Taylor, Ralf Weiskirchen
Summary: The research team has proposed a digital platform called '3R Blackboard' to facilitate the sharing of surplus biological materials from animals, aiming to reduce the number of animals used. Pilot study has shown that this platform is highly effective, resulting in a significant reduction in the number of animals used, as well as resource saving, knowledge exchange, and establishment of new collaborations.
LABORATORY ANIMALS
(2022)
Article
Medicine, General & Internal
Peter W. Horby, Guilherme Pessoa-Amorim, Natalie Staplin, Jonathan R. Emberson, Mark Campbell, Enti Spata, Leon Peto, Nigel J. Brunskill, Simon Tiberi, Victor Chew, Thomas Brown, Hasan Tahir, Beate Ebert, David Chadwick, Tony Whitehouse, Rahuldeb Sarkar, Clive Graham, J. Kenneth Baillie, Buddha Basnyat, Maya H. Buch, Lucy C. Chappell, Jeremy Day, Saul N. Faust, Raph L. Hamers, Thomas Jaki, Edmund Juszczak, Katie Jeffery, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, Richard Haynes, Martin J. Landray
Summary: In patients hospitalized with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.
Article
Biochemistry & Molecular Biology
Spyridoula-Angeliki Nikou, Chunsheng Zhou, James S. Griffiths, Natalia K. Kotowicz, Bianca M. Coleman, Mary J. Green, David L. Moyes, Sarah L. Gaffen, Julian R. Naglik, Peter J. Parker
Summary: The fungal pathogen Candida albicans secretes the peptide toxin candidalysin, which activates MAPK p38 and ERK pathways, leading to inflammatory response and immune activation. p38 pathway mainly promotes IL-6 release, Src pathway promotes EGFR phosphorylation, and ERK pathway promotes c-Fos activation and chemokine release.
Article
Medicine, General & Internal
Tapio Paljarvi, Julian Forton, Sierra Luciano, Kimmo Herttua, Seena Fazel
Summary: This study found that patients with asthma or allergic rhinitis had increased odds of adverse neuropsychiatric outcomes after montelukast initiation.
Article
Neurosciences
Sarah M. Carpanini, Megan Torvell, Ryan J. Bevan, Robert A. J. Byrne, Nikoleta Daskoulidou, Takashi Saito, Takaomi C. Saido, Philip R. Taylor, Timothy R. Hughes, Wioleta M. Zelek, B. Paul Morgan
Summary: Complement plays a role in synaptic pruning and synaptic loss in Alzheimer's disease, and the lytic membrane attack complex (MAC) is involved in this process. Experimental evidence shows that C1q, C3 fragments and MAC are increased in Alzheimer's disease mice, and inhibition of MAC formation can reduce synaptic loss.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Review
Microbiology
James S. Griffiths, Selinda J. Orr, Charles Oliver Morton, Juergen Loeffler, P. Lewis White
Summary: Invasive fungal disease (IFD) causes severe morbidity and mortality, and the number of IFD cases is increasing. Current IFD diagnosis relies on fungal biomarkers and clinical risk/presentation, but the diverse fungal species and diagnostic challenges lead to empirical anti-fungal treatment for high-risk patients. Recent studies have focused on host-derived biomarkers that can predict and identify IFD, enhancing diagnostic results. Once validated in larger studies, these biomarkers may optimize the clinical management of populations at risk of IFD.
Article
Respiratory System
Julian Legg, Jamie-Leigh Allen, Morag Andrew, Charlotte Annesley, Michelle Chatwin, Hannah Crawford, Joanna Elverson, Julian Forton, Kate Oulton, Kate Renton, Alison Tavare, Hilary Tedd, A. John Simpson
Article
Respiratory System
A. John Simpson, Jamie-Leigh Allen, Michelle Chatwin, Hannah Crawford, Joanna Elverson, Victoria Ewan, Julian Forton, Ronan McMullan, John Plevris, Kate Renton, Hilary Tedd, Rhys Thomas, Julian Legg
Article
Multidisciplinary Sciences
Lucy Allen, Lorna Allen, Siobhan B. Carr, Gwyneth Davies, Damian Downey, Marie Egan, Julian T. Forton, Robert Gray, Charles Haworth, Alexander Horsley, Alan R. Smyth, Kevin W. Southern, Jane C. Davies
Summary: With the introduction of small molecule, mutation-specific drugs, people with cystic fibrosis are undergoing transformative change as these drugs can restore function of the defective protein CFTR. However, not all genetic variants are suitable for mutation-specific drugs and these drugs also do not correct all the clinical manifestations of the disease. More research is needed to improve treatments for cystic fibrosis.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Yifan Wu, Shuqi Du, Lynn H. Bimler, Kelsey E. Mauk, Lea Lortal, Nessim Kichik, James S. Griffiths, Radim Osicka, Lizhen Song, Katherine Polsky, Lydia Kasper, Peter Sebo, Jill Weatherhead, J. Morgan Knight, Farrah Kheradmand, Hui Zheng, Jonathan P. Richardson, Bernhard Hube, Julian R. Naglik, David B. Corry
Summary: The fungal pathogen Candida albicans can enter the mouse brain from the blood and trigger two neuroimmune sensing mechanisms involving secreted as-partic proteinases (Saps) and candidalysin. The Saps disrupt the blood-brain barrier and promote fungal invasion, while candidalysin engages with microglia to defend against the fungus. These findings suggest that clearance of Candida albicans from the brain is achieved through innate immune mechanisms involving Saps, AD, candidalysin, and CD11b.
Article
Endocrinology & Metabolism
Peter W. Horby, Natalie Staplin, Leon Peto, Jonathan R. Emberson, Mark Campbell, Guilherme Pessoa-Amorim, Buddha Basnyat, Louise Thwaites, Rogier van Doorn, Raph L. Hamers, Jeremy Nel, John Amuasi, Manisha Rawal, Dipansu Ghosh, Jonathan Douse, Fergus Hamilton, Anthony Kerry, Pinky Thu-Ta, John Widdrington, Christopher A. Green, Purav Desai, Richard Stewart, Nguyen Thanh Phong, J. Kenneth Baillie, Maya Buch, Saul N. Faust, Thomas Jaki, Edmund Juszczak, Katie Jeffery, Marian Knight, Wei Shen Lim, Alan Montgomery, Aparna Mukherjee, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, Richard Haynes, Martin J. Landray
Summary: Empagliflozin is not associated with reduced mortality, hospital stay, or progression to invasive mechanical ventilation or death in hospitalized adults with COVID-19.
LANCET DIABETES & ENDOCRINOLOGY
(2023)
Article
Medicine, General & Internal
Peter W. Horby, Jonathan R. Emberson, Marion Mafham, Mark Campbell, Leon Peto, Guilhenne Pessoa-Amorim, Enti Spata, Natalie Staplin, Catherine Lowe, David R. Chadwick, Christopher Brightling, Richard Stewart, Paul Collini, Abdul Ashish, Christopher A. Green, Ben Prudon, Timothy Felton, Anthony Kerry, J. Kenneth Baillie, Maya H. Such, Jeremy Day, Saul N. Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Marian Knight, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Richard Haynes, Martin J. Landray
Summary: This study evaluated the use of baricitinib in the treatment of patients hospitalized with COVID-19. The results showed that baricitinib significantly reduced the risk of death, although the effect size was slightly smaller than previous trials. Overall evidence suggests that JAK inhibitors can reduce mortality in hospitalized COVID-19 patients by about 20%.