Article
Immunology
Felipe Silva de Franca, Isadora Maria Villas-Boas, Bruno Cogliati, Trent M. Woodruff, Edimara da Silva Reis, John D. Lambris, Denise V. Tambourgi
Summary: The study revealed that Naja annulifera venom can activate the complement system, leading to the release of lipid mediators and chemokines, and subsequent pathological reactions. Inhibition of the C5a-C5aR1 axis can mitigate the effects of complement activation. The cyclic peptide antagonist PMX205 can rescue mice from systemic reactions and prevent acute lung injury caused by complement activation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Carlos Arias-Cabrales, Eva Rodriguez-Garcia, Javier Gimeno, David Benito, Maria Jose Perez-Saez, Dolores Redondo-Pachon, Anna Buxeda, Carla Burballa, Marta Crespo, Marta Riera, Julio Pascual
Summary: The study investigated the role of C5a receptors in renal ischemia-reperfusion injury through in vitro models and human biopsies. The results showed that C5aR1 expression was significantly increased in acute injury, whereas C5L2 could be related to endothelial cell damage during the injury process.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
Klebea Carvalho, Nicole D. Schartz, Gabriela Balderrama-Gutierrez, Heidi Y. Liang, Shu-Hui Chu, Purnika Selvan, Angela Gomez-Arboledas, Tiffany J. Petrisko, Maria Fonseca, Ali Mortazavi, Andrea J. Tenner
Summary: The complement system plays a role in Alzheimer's disease by enhancing microglial activation pathways. Inhibition of C5aR1 may be a potential therapeutic strategy for treating Alzheimer's disease.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Multidisciplinary Sciences
Benjamin Nuerge, Alan Lennart Schulz, Daniel Kaemmerer, Joerg Saenger, Katja Evert, Stefan Schulz, Amelie Lupp
Summary: The complement component C5a and its receptor C5aR1 play crucial roles in the development of inflammatory diseases and are also widely expressed in various tumor entities, suggesting a potential as a future therapeutic target.
Article
Immunology
Shirin Emtenani, Maike M. Holtsche, Richard Stahlkopf, Daniel L. Seiler, Timothy Burn, Huiqing Liu, Melissa Parker, Kaan Yilmaz, Hasan O. Dikmen, Markus Huber Lang, Christian D. Sadik, Christian M. Karsten, Nina van Beek, Ralf J. Ludwig, Joerg Koehl, Enno Schmidt
Summary: This study reveals a complex landscape of activated complement receptors, complement factors, and related molecules in early Bullous pemphigoid (BP) skin lesions. The C5a/C5aR1 axis plays a pivotal role in attracting inflammatory cells to the skin in BP. Specific inhibition of C5aR1 reduces the migration of human neutrophils towards C5a, while stimulation of C5aR2 has no effect. These findings provide a basis for clinical studies targeting this axis in BP and other complement-mediated autoimmune disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Keqing Jiang, Shibang Lu, Dongxiao Li, Mingjiang Liu, Hu Jin, Biao Lei, Sifan Wang, Kang Long, Songqing He, Fudi Zhong
Summary: This study reveals that C5aR1 plays a crucial role in hepatic inflammation and fibrosis in NASH. The results show that C5 deficiency alleviates hepatic steatosis, fibrosis, and inflammation in NASH mice. Transcriptional profiling identifies several enriched pathways associated with C5aR1 deficiency. Overall, C5aR1 may be a potential target for drug development and therapeutic intervention in NASH.
JOURNAL OF GASTROENTEROLOGY
(2023)
Review
Cell Biology
Anna Ruocco, Anna Sirico, Rubina Novelli, Silvia Iannelli, Shane Vontelin Van Breda, Diego Kyburz, Paul Hasler, Andrea Aramini, Pier Giorgio Amendola
Summary: Bone remodeling is a dynamic process dependent on the functions of osteoblasts and osteoclasts. The complement system plays a crucial role in regulating the functions of these cells, particularly in inflammatory states. This review analyzes the role of the C5a-C5aR1 axis in bone physiology and pathophysiology, including its involvement in inflammatory bone diseases such as rheumatoid arthritis, osteoporosis and bone cancer metastasis. Furthermore, pharmacological approaches targeting C5aR1 for the treatment of these conditions are examined. The article highlights the importance of the C5a-C5aR1 axis as a therapeutic target for mediating interactions between the skeletal and immune systems, considering the growing interest in osteoimmunology and the lack of data on its role in bone pathophysiology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Carolina Pimenta-Lopes, Cristina Sanchez-de-Diego, Alexandre Deber, Andrea Egea-Cortes, Jose Antonio Valer, Albert Alcala, Andres Mendez-Lucas, Anna Esteve-Codina, Jose Luis Rosa, Francesc Ventura
Summary: Age-related and chemotherapy-induced bone loss is influenced by cellular senescence and the secretion of specific factors. The alternative complement system is found to play a central role in skeletal bone loss, with complement factor D being one of the most responsive factors. Osteoblasts and osteocytes activate complement, while monocytes and osteoclasts are the primary targets. Inhibition of the alternative complement pathway may have therapeutic benefits in osteopenic disorders.
Article
Medicine, Research & Experimental
Bruna M. Silva, Giovanni F. Gomes, Flavio P. Veras, Seppe Cambier, Gabriel V. L. Silva, Andreza U. Quadros, Diego B. Caetite, Daniele C. Nascimento, Camilla M. Silva, Juliana C. Silva, Samara Damasceno, Ayda H. Schneider, Fabio Beretta, Sabrina S. Batah, Icaro M. S. Castro, Isadora M. Paiva, Tamara Rodrigues, Ana Salina, Ronaldo Martins, Guilherme C. M. Cebinelli, Naira L. Bibo, Daniel M. Jorge, Helder I. Nakaya, Dario S. Zamboni, Luiz O. Leiria, Alexandre T. Fabro, Jose C. Alves-Filho, Eurico Arruda, Paulo Louzada-Junior, Rene D. Oliveira, Larissa D. Cunha, Pierre Van Mol, Lore Vanderbeke, Simon Feys, Els Wauters, Laura Brandolini, Andrea Aramini, Fernando Q. Cunha, Joerg Koehl, Marcello Allegretti, Diether Lambrechts, Joost Wauters, Paul Proost, Thiago M. Cunha
Summary: Activation of the C5a/C5aR1 pathway in COVID-19 patients can worsen the disease and lead to cytokine storm syndrome, organ dysfunction, and death. Inhibiting C5aR1 signaling can improve lung immunopathology, suggesting that C5aR1 antagonists may be useful for COVID-19 treatment.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Jasmin Maria Buelow, Nikolai Renz, Melanie Haffner-Luntzer, Verena Fischer, Astrid Schoppa, Jan Tuckermann, Joerg Koehl, Markus Huber-Lang, Anita Ignatius
Summary: Recent evidence suggests that the complement system may play a role in bone homeostasis and inflammatory bone loss. This study demonstrated that the C5aR1 receptor on osteoblasts is crucial for the development of postmenopausal osteoporosis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sandeep Silawal, Benjamin Kohl, Jingjian Shi, Gundula Schulze-Tanzil
Summary: The study found that C5a stimulation did not affect cell survival, but had a significant impact on the gene expression of C5aR, CRPs, and inflammatory cytokines at different stages. C5a may directly contribute to cell activation, thereby being involved in tendon healing and tendinopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Francois Marceau, Eric Petitclerc
Summary: The newly approved drug avacopan by the FDA is an orally bioavailable treatment for the rare disease ANCA-associated vasculitis, targeting inflammation-induced small vessel vasculitis by inhibiting the effects of C5a on vascular tissues through C5aR1 blockade.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aurosikha Das, Manaswini Ghosh, Pulkit Kr. Gupta, Soumendra Rana
Summary: The complement system is crucial in immune response and plays an important role in physiology and pathophysiology. C5a, one of the most potent anaphylatoxins, triggers pro-inflammatory responses by binding to complement receptors. Targeting C5a with small molecule drugs can potentially modulate its destructive signaling response under pathological conditions.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Xueqin Li, Xin Chen, Shengzhe Gong, Jie Zhao, Chen Yao, Hanyong Zhu, Rui Xiao, Yongqin Qin, Rongqing Li, Na Sun, Xiangyang Li, Fuxing Dong, Tingting Zhao, Yuchen Pan, Jing Yang
Summary: In this study, it was found that an increase in platelet levels in colorectal cancer (CRC) patients promotes tumor growth. Platelets signal tumor-associated macrophages (TAMs) through CD62P binding to PSGL-1, activating the JNK/STAT1 signaling pathway, leading to the transcription of the C5 gene and release of C5a. This promotes TAMs towards a pro-tumor phenotype. The results provide a potential therapeutic strategy for CRC patients.
Review
Immunology
Vladimir Tesar, Zdenka Hruskova
Summary: The alternative complement pathway plays an important role in the treatment of AAV. Avacopan shows similar efficacy and better safety compared to high-dose corticosteroids in the induction treatment of AAV.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Endocrinology & Metabolism
Tanya S. McDonald, Titaya Lerskiatiphanich, Trent M. Woodruff, Pamela A. McCombe, John D. Lee
Summary: Neurodegeneration refers to the progressive loss of neurons in disorders like Alzheimer's, Huntington's, and Parkinson's disease. Energy metabolism disturbances and alterations are common features in the onset and progression of these diseases. Understanding these metabolic changes could lead to improved treatment options for neurodegenerative disorders.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Eduardo A. Albornoz, Alberto A. Amarilla, Naphak Modhiran, Sandra Parker, Xaria X. Li, Danushka K. Wijesundara, Julio Aguado, Adriana Pliego Zamora, Christopher L. D. McMillan, Benjamin Liang, Nias Y. G. Peng, Julian D. J. Sng, Fatema Tuj Saima, Jenny N. Fung, John D. Lee, Devina Paramitha, Rhys Parry, Michael S. Avumegah, Ariel Isaacs, Martin W. Lo, Zaray Miranda-Chacon, Daniella Bradshaw, Constanza Salinas-Rebolledo, Niwanthi W. Rajapakse, Ernst J. Wolvetang, Trent P. Munro, Alejandro Rojas-Fernandez, Paul R. Young, Katryn J. Stacey, Alexander A. Khromykh, Keith J. Chappell, Daniel Watterson, Trent M. Woodruff
Summary: COVID-19 infection may lead to neurological symptoms similar to Parkinson's disease. The study found that SARS-CoV-2 and spike protein can directly activate the NLRP3 inflammasome in microglial cells, which may contribute to the development of neuroinflammation.
MOLECULAR PSYCHIATRY
(2023)
Article
Chemistry, Multidisciplinary
Luyao Sun, Wendong Gao, Jingjing Wang, Xueming Niu, Nyoman Kurniawan, Li Li, Zhi Ping Xu
Summary: This study presents a new type of sono-chemo sensitizer based on a manganese (Mn)-layered double hydroxide-based defect-rich nanoplatform. This nanoplatform efficiently triggers reactive oxygen species generation for enhanced sono/chemo-dynamic therapy. It also relieves tumor hypoxia and produces augmented singlet oxygen by catalyzing endogenous H2O2. Additionally, the released Mn2+ ions and immune-modulating agent intensify immune activation and reverse the immunosuppressive tumor microenvironment. Overall, this nanoplatform demonstrates excellent anti-tumor efficacy and provides a new strategy for synergistic combination cancer therapy by functionalizing nanoparticles as sono-chemo sensitizers.
Article
Neuroimaging
Nien-Chu Shih, Nyoman D. Kurniawan, Ryan P. Cabeen, Laura Korobkova, Ellen Wong, Helena C. Chui, Kristi A. Clark, Carol A. Miller, Debra Hawes, Kymry T. Jones, Farshid Sepehrband
Summary: In this study, ex vivo multi-parameter quantitative MRI measures were acquired in human specimens using a 16.4 Tesla scanner. Correlation analyses with histological measurements revealed significant correlations between the quantitative MRI measures and neurofilament and phosphorylated Tau density, indicating sensitivity to layer-specific changes in the dentate gyrus of Alzheimer's disease tissues.
NEUROIMAGE-CLINICAL
(2023)
Article
Immunology
Xaria X. Li, John D. Lee, Han S. Lee, Richard J. Clark, Trent M. Woodruff
Summary: TLQP-21 is a neuropeptide derived from the VGF precursor protein and has pleiotropic roles in regulating metabolism, nociception, and microglial functions. TLQP-21 acts through several receptors, with C3aR being the most commonly reported. However, its activity in immune cells, which express C3aR, remains understudied. This study found that TLQP-21 induced ERK signaling in human and mouse macrophages, with mouse TLQP-21 being more potent than the human counterpart. These findings suggest a significant discrepancy in TLQP-21 C3aR activity between human and murine receptors in immune cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Wen-Sung Chung, Alejandra Lopez-Galan, Nyoman D. Kurniawan, N. Justin Marshall
Summary: This study provides the first detailed description of the neuroanatomical features of a tropical and diurnal cuttlefish and investigates ontogenetic changes in its visual and learning centers. Comparisons with other cuttlefish species are made to construct a connectivity map of the cuttlefish brain. The findings reveal brain anatomy differences and previously unknown neural connections associated with camouflage, motor control, and chemosensory function.
Article
Oncology
Andrew O. Yam, Jacqueline Bailey, Francis Lin, Arnolda Jakovija, Scott E. Youlten, Claudio Counoupas, Matthias Gunzer, Tobias Bald, Trent M. Woodruff, James A. Triccas, Leonard D. Goldstein, David Gallego-Ortega, Shane T. Grey, Tatyana Chtanova
Summary: Intratumoral injection of microbial bioparticles stimulates neutrophil antitumor functions, leading to remodeling of tumor tissue, repression of tumor growth, and enhancement of checkpoint inhibitor therapy. This indicates the potential of microbial therapy in the treatment of solid cancers.
Article
Biophysics
Abdullah A. A. Althobity, Nemat Khan, Cheyenne J. J. Sandrock, Trent M. M. Woodruff, Gary J. J. Cowin, Ian M. M. Brereton, Nyoman D. D. Kurniawan
Summary: In this study, pathological changes in the lumbar spinal cord of EAE mice were investigated using 9.4-T MRI. Changes in MRI biomarker signatures were identified that can be useful in evaluating the efficacy of novel drugs using EAE models in vivo.
NMR IN BIOMEDICINE
(2023)
Editorial Material
Cell Biology
Eduardo A. Albornoz, Richard Gordon, Vinod Kumar, Avril A. B. Robertson, Kate Schroder, Trent M. Woodruff
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Editorial Material
Neurosciences
Fatima Nasrallah, Nyoman D. Kurniawan
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemical Research Methods
Xaria X. Li, Trent M. Woodruff
Summary: This study presents a protocol for investigating the effects of C3aR and C5aR1 receptors in vitro using phosphorylated ERK as a readout. The protocol includes steps for isolating human monocyte-derived macrophages, culturing and preparing cell lines expressing the receptors, performing pharmacological assays, and detecting phospho-ERK1/2.
Article
Cell Biology
Julio Aguado, Alberto A. Amarilla, Atefeh Taherian Fard, Eduardo A. Albornoz, Alexander Tyshkovskiy, Marius Schwabenland, Harman K. Chaggar, Naphak Modhiran, Cecilia Gomez-Inclan, Ibrahim Javed, Alireza A. Baradar, Benjamin Liang, Lianli Peng, Malindrie Dharmaratne, Giovanni Pietrogrande, Pranesh Padmanabhan, Morgan E. Freney, Rhys Parry, Julian D. J. Sng, Ariel Isaacs, Alexander A. Khromykh, Guillermo Valenzuela Nieto, Alejandro Rojas-Fernandez, Thomas P. Davis, Marco Prinz, Bertram Bengsch, Vadim N. Gladyshev, Trent M. Woodruff, Jessica C. Mar, Daniel Watterson, Ernst J. Wolvetang
Summary: Senescent cells play a significant role in brain aging and COVID-19-induced neuropathology, and senolytic therapy shows therapeutic potential in protecting against COVID-19-induced brain aging.
Article
Neurosciences
Xuan Vinh To, Nyoman D. Kurniawan, Paul Cumming, Fatima A. Nasrallah
Summary: In this study, the researchers compared in vivo and ex vivo imaging measures in a mouse model of concussion. The results showed poor agreement between the two methods in assessing the structural integrity of the brain affected by concussion. Furthermore, the comparison revealed completely opposite and contradictory results between in vivo and ex vivo imaging, highlighting the need for caution when extrapolating ex vivo imaging findings to physiological measurements in vivo.
Meeting Abstract
Biochemistry & Molecular Biology
John Lee, Jianina Marallag, Trent Woodruff
MOLECULAR IMMUNOLOGY
(2022)