Article
Immunology
Caroline B. K. Mathiesen, Asha M. Rudjord-Levann, Monika Gad, Jesper Larsen, Finn Sellebjerg, Anders Elm Pedersen
Summary: Cladribine has shown to reduce the inflammatory potential and phagocytic activity of M1 macrophages without affecting the differentiation or phenotype of these cells in relevant therapeutic concentrations in vitro. This could have a beneficial clinical impact in the treatment of MS by reducing plaque development while leaving M1 macrophages intact for protection against infections.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Lingzhi Wang, Catarina Oliveira, Qiu Li, Andreia S. Ferreira, Claudia Nunes, Manuel A. Coimbra, Rui L. Reis, Albino Martins, Chunming Wang, Tiago H. Silva, Yanxian Feng
Summary: This study characterized a pharmaceutical-grade fucoidan extracted from Fucus vesiculosus and investigated its anti-inflammatory potential. The extract contained mainly fucose, followed by uronic acids, galactose, and xylose, with a molecular weight of 70 kDa and a sulfate content of around 10%. In vitro and in vivo experiments demonstrated the ability of the fucoidan extract to modulate cytokine expression and reverse inflammation induced by lipopolysaccharide.
Article
Chemistry, Multidisciplinary
Giulia Torrieri, Imran Iqbal, Flavia Fontana, Virpi Talman, Heidi Liljenback, Andriana Putri, Wail Nammas, Johan Rajander, Xiang Guo-Li, Philip S. S. Low, Tambet Teesalu, Anne Roivainen, Jouni Hirvonen, Heikki Ruskoaho, Vimalkumar Balasubramanian, Antti Saraste, Helder A. Santos
Summary: Myocardial infarction (MI) is a major cause of death worldwide, and current therapies are insufficient in restoring injured heart tissue. Nanomedicines offer a potential solution, but targeting the heart tissue remains a challenge. In this study, a MI-selective precision nanosystem using atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages was developed. The system showed biocompatibility with cardiac cells and ANP receptor-dependent interaction with cardiomyocytes. Furthermore, the delivery of nanoparticles loaded with self-renewal promoting compounds resulted in increased cell proliferation. The study demonstrates the development of a peptide-guided precision nanosystem for targeted delivery of therapeutic compounds to the infarcted heart.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Dentistry, Oral Surgery & Medicine
Yingyi Chen, Yitong Liu, Huan Xia, Guiyang Xia, Junji Xu, Sheng Lin, Lijia Guo, Yi Liu
Summary: In this study, the effect of Litcubanine A (LA) on macrophage chemotaxis and osteoclast differentiation in periodontitis was investigated. LA was found to inhibit macrophage chemotaxis and suppress osteoclast differentiation through the MAPK signaling pathway, resulting in lower bone loss in a ligature-induced periodontitis model. Thus, LA shows promise as a potential therapeutic agent for periodontitis.
JOURNAL OF PERIODONTAL RESEARCH
(2023)
Article
Cell Biology
Qiuhua Yang, Qian Ma, Jiean Xu, Zhiping Liu, Jianqiu Zou, Jian Shen, Yaqi Zhou, Qingen Da, Xiaoxiao Mao, Sarah Lu, David J. Fulton, Neal L. Weintraub, Zsolt Bagi, Mei Hong, Yuqing Huo
Summary: The deficiency of Prkaa1 in myeloid cells impacts the expression of genes involved in glucose and lipid metabolism, compromises macrophages' metabolic abilities, reduces their recruitment in various tissues, and ultimately leads to a deceleration in the development of related metabolic disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Zhongyuan Lin, Changliang Luo, Yulin Yuan
Summary: This study explored the predictive value of the monocyte to apolipoprotein A1 ratio (MAR) and its relationship with clinicopathological staging in breast cancer (BC). The results showed that MAR can distinguish between BC and benign breast disease, and it is an independent risk factor for BC. High levels of MAR are associated with late staging and tumor invasion depth of BC. Therefore, MAR is a potentially valuable predictor of BC and further studies are needed to explore its clinical value.
CANCER MANAGEMENT AND RESEARCH
(2023)
Article
Engineering, Biomedical
Guangzhao Tian, Shuangpeng Jiang, Junqi Li, Fu Wei, Xu Li, Yi Ding, Zhen Yang, Zhiqiang Sun, Kangkang Zha, FuXin Wang, Bo Huang, Liqing Peng, Qiuming Wang, Zhuang Tian, Xi Yang, Zhigang Wang, Quanyi Guo, Weimin Guo, Shuyun Liu
Summary: This study demonstrates that pepsin-solubilized DCM (PDCM) can activate bone marrow-derived macrophages to polarize towards a beneficial macrophage phenotype. These polarized macrophages promote bone marrow-derived mesenchymal stem cell invasion, migration, proliferation, and chondrogenic differentiation. Combining DCM scaffolds with early intra-articular injection of IL-4 creates a wound-healing microenvironment that enhances cartilage regeneration in a rat knee osteochondral defect model.
ACTA BIOMATERIALIA
(2021)
Article
Food Science & Technology
Yaozhong Hu, Jiaxin Gu, Jing Lin, Yi Wang, Feier Yang, Jia Yin, Zhenting Yu, Sihao Wu, Huan Lv, Xuemeng Ji, Shuo Wang
Summary: The intervention of EGCG on macrophage polarization was found to promote M2 polarization and inhibit M1 polarization, particularly in liver, colon, spleen, and brain.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Multidisciplinary Sciences
Julie Rondeaux, Deborah Groussard, Sylvanie Renet, Virginie Tardif, Anais Dumesnil, Alphonse Chu, Lea Di Maria, Theo Lemarcis, Manon Valet, Jean-Paul Henry, Zina Badji, Claire Vezier, Delphine Beziau-Gasnier, Annette E. Neele, Menno P. J. de Winther, Dominique Guerrot, Marjorie Brand, Vincent Richard, Eric Durand, Ebba Brakenhielm, Sylvain Fraineau
Summary: Epigenetic regulation of histone H3K27 methylation plays a key role in cardiac repair after myocardial infarction. The authors demonstrate the ectopic EZH2 and cytoplasmic inactive localization of EZH2 during monocyte differentiation and in immunomodulatory cardiac macrophages. Pharmacological inhibition of EZH2 resolves H3K27 methylation, enhances gene expression, and accelerates cardiac inflammatory resolution, preventing infarct expansion and cardiac dysfunction.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Yuchen Hua, Jinjie Wu, Hongfeng Wu, Cheng Su, Xiangfeng Li, Qiang Ao, Qin Zeng, Xiangdong Zhu, Xingdong Zhang
Summary: The study reveals that HANPs can induce TLR4 signaling activation and synergize with LPS to promote macrophage polarization toward M1 phenotype, as well as to abolish immune tolerance in response to repeated LPS stimulation.
ACTA BIOMATERIALIA
(2021)
Article
Immunology
Huayang Wang, Qibing Huang, Zhijie Zhang, Jian Ji, Tao Sun, Donghai Wang
Summary: The study found that CXCR2 is transiently overexpressed in peripheral monocytes of TBI patients post-surgery, which is associated with unfavorable outcomes. Serum and CSF from TBI patients promote CXCR2 expression in monocytes, and CXCR2 antagonist can decrease monocyte chemotaxis.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Immunology
Clarissa Leal Silva e Souza, Camila Dutra Barbosa, Hanna I. L. N. Coelho, Manoel N. N. Santos Junior, Elaine Novaes Barbosa, Ellunny Chaves Queiroz, Mauro Fernandes Teles, Deborah Cruz dos Santos, Rafaela Souza Bittencourt, Telma de Jesus Soares, Marcio Vasconcelos Oliveira, Jorge Timenetsky, Guilherme Barreto Campos, Lucas Miranda Marques
Summary: The study investigated the influence of 17 beta-estradiol on the monocyte/macrophage response induced by S. aureus in in vitro models, finding that E2 can inhibit the production of proinflammatory cytokines and reduce the expression of TLR2.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kun-Tsan Lee, Chin-Horng Su, Shan-Chi Liu, Bo-Cheng Chen, Jun-Way Chang, Chun-Hao Tsai, Wei-Chien Huang, Chin-Jung Hsu, Wei-Cheng Chen, Yang-Chang Wu, Chih-Hsin Tang
Summary: This study revealed that there are higher levels of M1 macrophage markers and ICAM-1 in synovium tissue from patients with osteoarthritis compared to healthy controls. Cordycerebroside A was found to inhibit the synthesis of ICAM-1 and prevent M1 macrophage adhesion to synovial fibroblasts in osteoarthritis. This demonstrates that cordycerebroside A has novel anti-osteoarthritis effects.
JOURNAL OF FOOD BIOCHEMISTRY
(2022)
Article
Immunology
Steven P. Cass, Olivia Mekhael, Danya Thayaparan, Joshua J. C. McGrath, Spencer D. Revill, Matthew F. Fantauzzi, Peiyao Wang, Amir Reihani, Aaron Hayat, Christopher S. Stevenson, Anna Dvorkin-Gheva, Fernando M. Botelho, Martin R. Stampfli, Kjetil Ask
Summary: Cigarette smoke exposure altered the composition of pulmonary macrophages by expanding CD11b(+) subpopulations. These compositional changes were associated with attenuated fibrogenesis, as well as predominant M1 polarization and decreased fibrotic activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Jose J. Rivera Rivas, Charles J. Czuprynski
Summary: Histophilus somni is a Gram-negative coccobacillus that causes diffuse vasculitis and intravascular thrombosis in cattle. Our study demonstrates that exposure to H. somni cells causes monocyte-derived macrophages to release microparticles with pro-coagulant activity, potentially amplifying thrombus formation.
VETERINARY MICROBIOLOGY
(2022)
Article
Biology
Annabell Roberti, Laura Elizabeth Chaffey, David R. Greaves
Summary: NF-kappa B plays a central role in inflammation, response to DNA damage, and oxidative stress, with dysregulation implicated in various human diseases. Clinical efforts are underway to investigate modulation of NF-kappa B signaling for treating chronic inflammatory conditions.
Article
Hematology
Martina Colicchia, Waltraud C. Schrottmaier, Gina Perrella, Jasmeet S. Reyat, Jenefa Begum, Alexandre Slater, Joshua Price, Joanne C. Clark, Zhaogong Zhi, Megan J. Simpson, Joshua H. Bourne, Natalie S. Poulter, Abdullah O. Khan, Phillip L. R. Nicolson, Matthew Pugh, Paul Harrison, Asif J. Iqbal, George E. Rainger, Steve P. Watson, Mark R. Thomas, Nicola J. Mutch, Alice Assinger, Julie Rayes
Summary: S100A8/A9, secreted by activated myeloid cells, has antimicrobial, proinflammatory, and prothrombotic properties. Increased levels of S100A8/A9 in COVID-19 patients are associated with poor outcomes. S100A8/A9 is mainly detected in neutrophils and deposited on vessel walls in COVID-19 lungs. Platelets interact with S100A8/A9, leading to the formation of procoagulant platelets.
Article
Oncology
Miguel Guerra-Rodriguez, Priscila Lopez-Rojas, Angel Amesty, Haidee Aranda-Tavio, Yeray Brito-Casillas, Ana Estevez-Braun, Leandro Fernandez-Perez, Borja Guerra, Carlota Recio
Summary: About 70% of breast tumors are estrogen receptor (ER)-positive and depend on estrogens and their ER for growth and survival. Current therapeutic treatment has limitations and there is a need for new drugs that modulate ER activity. This study identified two compounds with potential antitumoral effects and low estrogenic activity, offering a pharmacological opportunity for treatment of ER-positive breast cancer.
Article
Cardiac & Cardiovascular Systems
Surawee Chuaiphichai, Sandy M. Chu, Ricardo Carnicer, Matthew Kelly, Jenifer K. Bendall, Jillian N. Simon, Gillian Douglas, Mark J. Crabtree, Barbara Casadei, Keith M. Channon
Summary: This study reveals a critical role for endothelial cell Gch1/BH4 biosynthesis in coronary vascular function and cardiac function. Loss of cardiac endothelial cell BH4 leads to coronary vascular dysfunction, reduced functional recovery, and increased myocardial infarct size following ischemia/reperfusion injury. Targeting endothelial cell Gch1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of cardiac dysfunction, ischemia injury, and heart failure.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Franziska Krautter, Mohammed T. Hussain, Zhaogong Zhi, Danielle R. Lezama, Julia E. Manning, Emily Brown, Noemi Marigliano, Federica Raucci, Carlota Recio, Myriam Chimen, Francesco Maione, Alok Tiwari, Helen M. McGettrick, Dianne Cooper, Edward A. Fisher, Asif J. Iqbal
Summary: This study reveals the pathological role of Gal-9 in promoting monocyte recruitment and atherosclerotic plaque progression, making it a novel target in the prevention of plaque formation and progression.
Editorial Material
Cardiac & Cardiovascular Systems
Tomasz J. Guzik, Keith M. Channon
EUROPEAN HEART JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Valentina Vellecco, Anella Saviano, Federica Raucci, Gian Marco Casillo, Adel Abo Mansour, Elisabetta Panza, Emma Mitidieri, Grazia Daniela Femminella, Nicola Ferrara, Giuseppe Cirino, Raffaella Sorrentino, Asif Jilani Iqbal, Roberta d'Emmanuele di Villa Bianca, Mariarosaria Bucci, Francesco Maione
Summary: This study aimed to evaluate the impact of IL17Ab treatment on peripheral features of Alzheimer's disease, such as systemic inflammation, peripheral vascular dysfunction, and related pro-thrombotic state. The results showed that IL17Ab treatment could alleviate these AD features and exhibit systemic and peripheral protective effects.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Immunology
Laleh Pezhman, Sophie J. Hopkin, Jenefa Begum, Silke Heising, Daniela Nasteska, Mussarat Wahid, G. Ed Rainger, David J. Hodson, Asif J. Iqbal, Myriam Chimen, Helen M. McGettrick
Summary: In this study, we demonstrate the therapeutic potential of the immunopeptide PEPITEM in mitigating the pathological impact of obesity, such as low-grade inflammation and pancreatic dysfunction. Further research is needed to assess its efficacy in reducing obesity-related co-morbidities, particularly in high-risk individuals struggling with weight control through lifestyle modifications. This study highlights the importance of targeting cellular and molecular processes in obesity for effective management and presents PEPITEM as a novel therapeutic option.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Physiology
Sandy M. Chu, Lisa C. Heather, Surawee Chuaiphichai, Thomas Nicol, Benjamin Wright, Matthieu Miossec, Jennifer K. Bendall, Gillian Douglas, Mark J. Crabtree, Keith M. Channon
Summary: This study discovered the physiological role of cardiomyocyte-derived tetrahydrobiopterin (BH4) in cardiac metabolism and stress response. Deletion of BH4 synthesis in hearts shifted substrate preference from fatty acid to glucose and showed a protective effect in response to ischaemia-reperfusion (IR) injury. Manipulating fatty acid metabolism via BH4 availability could be a therapeutic strategy for limiting IR injury.
EXPERIMENTAL PHYSIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Surawee Chuaiphichai, Yasmin Dickinson, Christopher A. R. Whiteman, Desson Au-Yeung, Eileen McNeill, Keith M. Channon, Gillian Douglas
Summary: This study investigated the role and mechanisms of endothelial cell-mediated vaso-relaxation function in pregnancy outcomes. The results showed that maternal endothelial cell tetrahydrobiopterin (BH4) deficiency is associated with increased blood pressure, enhanced vasoconstriction, and reduced endothelial-dependent vasodilation in late pregnancy. Supplementation with reduced folates may help restore endothelial cell vasodilator function and prevent/treat pregnancy-related hypertension.
VASCULAR PHARMACOLOGY
(2023)
Article
Rheumatology
Anella Saviano, Adel Abo Manosour, Federica Raucci, Francesco Merlino, Noemi Marigliano, Anna Schettino, Mussarat Wahid, Jenefa Begum, Andrew Filer, Julia E. Manning, Gian Marco Casillo, Marialuisa Piccolo, Maria Grazia Ferraro, Simona Marzano, Pasquale Russomanno, Rosa Bellavita, Carlo Irace, Jussara Amato, Mohammed Alfaifi, Peter Rimmer, Tariq Iqbal, Stefano Pieretti, Valentina Vellecco, Francesco Caso, Luisa Costa, Roberto Giacomelli, Raffaele Scarpa, Giuseppe Cirino, Mariarosaria Bucci, Helen M. McGettrick, Paolo Grieco, Asif Jilani Iqbal, Francesco Maione
Summary: This study identified a novel IL-17A/F-derived peptide and generated a new anti-IL-17 antibody that can effectively reverse the pro-inflammatory actions of IL-17A/F. The antibody showed less off-target effects compared to the current gold-standard biologic. Preclinical and clinical evidence demonstrated the high efficacy and therapeutic potency of the antibody in patients with IMIDs.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Pharmacology & Pharmacy
Vincent B. Luscombe, Luis Alberto Baena-Lopez, Carole J. R. Bataille, Angela J. Russell, David R. Greaves
Summary: In this study, heterologous cell lines with low GPR84 expression levels were developed to mimic the response of primary cells in a label-free cell electrical impedance sensing system. It was found that DL-175 exhibited a delayed impedance response, a delayed and suppressed activation of Akt, and impaired ability to internalise GPR84 from the plasma membrane compared to 6-OAU. These signalling differences were transient and occurred only at early time points in the low expressing cell lines, highlighting the importance of receptor number and kinetic readouts when evaluating signalling bias. These findings provide new insights into GPR84 signalling and the evaluation of newly developed agonists.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Joshua H. Bourne, Joana Campos, Sophie J. Hopkin, Katharine Whitworth, James Palis, Yotis A. Senis, Julie Rayes, Asif J. Iqbal, Alexander Brill
Summary: NLRP3 inflammasome plays an important role in megakaryocytes and platelets. By studying Nlrp3(A350V/+)/Gp1ba-Cre(KI/+) mice with a mutation similar to human Muckle-Wells syndrome, it was found that hyperactivation of the NLRP3 inflammasome leads to mild anemia and increased extramedullary erythropoiesis, promoting the acute inflammatory response.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Hongmei Fu, Juho Vuononvirta, Silvia Fanti, Fabrizia Bonacina, Antonio D'Amati, Guosu Wang, Thanushiyan Poobalasingam, Maria Fankhaenel, Davide Lucchesi, Rachel Coleby, David Tarussio, Bernard Thorens, Robert J. Hearnden, M. Paula Longhi, Paul Grevitt, Madeeha H. Sheikh, Egle Solito, Susana A. Godinho, Michele Bombardieri, David M. Smith, Dianne Cooper, Asif J. Iqbal, Jeffrey C. Rathmell, Samuel Schaefer, Valle Morales, Katiuscia Bianchi, Giuseppe Danilo Norata, Federica M. Marelli-Berg
Summary: T cell activation requires increased glucose uptake and engagement of the glycolytic pathway. In this study, researchers found that the glucose transporter 2 (Glut2) plays a key role in regulating the development of CD8(+) T cell effector responses in mice. Glut2 expression is influenced by environmental factors and is regulated by molecular interactions. Furthermore, human T cells also rely on Glut2, making it a potential target for therapeutic immunomodulation.
Article
Cell Biology
Sophie J. Hopkin, Laleh Pezhman, Jenefa Begum, Dean Kavanagh, Helen M. Mcgettrick, Asif J. Iqbal, Myriam Chimen
Summary: Aging is associated with increased systemic inflammation and loss of immune system function. Leukocyte trafficking is affected by aging, particularly in the peritoneal cavity. In aged female mice, there is an increase in leukocyte population within the peritoneal cavity, accompanied by an increase in inflammatory environment and changes in vascular structure, which may contribute to increased leukocyte migration to the cavity. These findings indicate that aging and sex influence leukocyte trafficking in a unique manner.
JOURNAL OF LEUKOCYTE BIOLOGY
(2023)