Article Immunology
Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles
Patrick P. G. Mulder, Marcel Vlig, Bouke K. H. L. Boekema, Matthea M. Stoop, Anouk Pijpe, Paul P. M. van Zuijlen, Evelien de Jong, Bram van Cranenbroek, Irma Joosten, Hans J. P. M. Koenen, Magda M. W. Ulrich
Summary: Severe burn injury induces persistent systemic inflammation marked by continuous release of immature neutrophils and shifts in T cell composition toward a more pro-inflammatory phenotype.
FRONTIERS IN IMMUNOLOGY (2021)
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Article Immunology
Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study
Astrid Fabri, Khalil Kandara, Remy Coudereau, Morgane Gossez, Paul Abraham, Celine Monard, Martin Cour, Thomas Rimmele, Laurent Argaud, Guillaume Monneret, Fabienne Venet
Summary: The study analyzed the impact of IL-10 production in septic patients' whole blood, revealing monocytes and CD4+ T cells as the main IL-10 producers associated with global immunosuppression in septic shock. Further research is needed to determine the pathophysiological mechanisms leading to increased IL-10 production in monocytes and CD4+ T cells.
FRONTIERS IN IMMUNOLOGY (2021)
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Article Immunology
An Unbiased Flow Cytometry-Based Approach to Assess Subset-Specific Circulating Monocyte Activation and Cytokine Profile in Whole Blood
Jurij Kiefer, Johannes Zeller, Balazs Bogner, Isabel A. ho*rbrand, Friederike Lang, Emil Deiss, Oscar Winninger, Mark Fricke, Sheena Kreuzaler, Eva Smudde, Markus Huber-Lang, Karlheinz Peter, Kevin J. Woollard, Steffen U. Eisenhardt
Summary: This paper presents a flow cytometry-based protocol for evaluating subset-specific activation and cytokine expression of circulating blood monocytes in humans and rats, offering an unbiased functional endpoint analysis for studying the differential regulation of monocytes in inflammatory and allogeneic immune responses.
FRONTIERS IN IMMUNOLOGY (2021)
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Article Immunology
Amelioration of Lupus Serum-Induced Skin Inflammation in CD64-Deficient Mice
Lijuan Jiang, Xiaoxiao Han, Wenlin Qiu, Tong Yu, Ruizhi Feng, Xuefei Wang, Xiaoru Duan, Guo-Min Deng
Summary: This study investigated the role of CD64 in SLE patients and animal models. The results showed that CD64 expression was increased in SLE patients and correlated with SLE progression and related indicators. In animal models, CD64 was associated with lupus pathogenesis and played a regulatory role in skin inflammation induced by lupus serum.
FRONTIERS IN IMMUNOLOGY (2022)
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Review Biology
Cellular Immuno-Profile in Septic Human Host: A Scoping Review
Christian Zanza, Giorgia Caputo, Gilda Tornatore, Tatsiana Romenskaya, Andrea Piccioni, Francesco Franceschi, Marco Artico, Samanta Taurone, Gabriele Savioli, Yaroslava Longhitano
Summary: Innate and adaptive immune system cells are crucial in the host response to sepsis. Changes in neutrophils and monocytes accompany sepsis, with potential impact on clinical outcomes. Recent research delves into techniques for studying circulating leukocytes and potential treatments for sepsis.
BIOLOGY-BASEL (2022)
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Review Biochemistry & Molecular Biology
Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis
Gara Arteaga-Henriquez, Jorge Lugo-Marin, Laura Gisbert, Imanol Setien-Ramos, Monica Martinez-Gallo, Ricardo Pujol-Borrell, Josep Antoni Ramos-Quiroga
Summary: Individuals with Autism spectrum disorder (ASD) exhibit differences in immune cell levels and inflammation markers compared to typically developing (TD) controls.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)
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Article Biochemistry & Molecular Biology
Monocyte Phenotypes and Physical Activity in Patients with Carotid Atherosclerosis
Mathilde Mura, Michele Weiss-Gayet, Nellie Della-Schiava, Erica Chirico, Patrick Lermusiaux, Marie Chambion-Diaz, Camille Faes, Anaelle Boreau, Benedicte Chazaud, Antoine Millon, Vincent Pialoux
Summary: Atherosclerosis is associated with chronic inflammation involving circulating monocytes. Physical activity has been shown to decrease inflammation and the risk of stroke. This study found that moderately active patients had a lower percentage of classical and intermediate monocytes compared to non-active and highly active patients. In contrast, the percentage of non-classical monocytes increased in moderately active patients. These findings suggest that physical activity can be beneficial for patients by reducing the risk of ischemic stroke and promoting lesion healing.
ANTIOXIDANTS (2022)
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Article Biochemistry & Molecular Biology
KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models
James D. West, Eric D. Austin, Elise M. Rizzi, Ling Yan, Harikrishna Tanjore, Amber L. Crabtree, Christy S. Moore, Gladson Muthian, Erica J. Carrier, David A. Jacobson, Rizwan Hamid, Peggy L. Kendall, Susan Majka, Anandharajan Rathinasabapathy
Summary: Loss of function KCNK3 mutation alters various physiological processes through inflammation, affecting factors such as inflammation and metabolism in response to hypoxia, dysregulation of bone marrow cells, and the role of inflammation in driving pulmonary arterial hypertension (PAH). Studies on both animal models and human samples suggest that altered circulating immune cells may play a key role in driving PAH susceptibility in patients with KCNK3 mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)
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Article Pharmacology & Pharmacy
G6PD is a critical enabler of hypoxia-induced accumulation of macrophages and platelets in mice lungs and contributor to lung inflammation
Ryota Hashimoto, Sachin A. Gupte
Summary: Platelets and macrophages may play a role in the pathogenesis of hypoxia-induced pulmonary hypertension, and targeting G6PD activity inhibitor could reduce lung inflammation.
VASCULAR PHARMACOLOGY (2022)
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Article Oncology
Philadelphia-negative myeloproliferative neoplasms display alterations in monocyte subpopulations frequency and immunophenotype
Vitor Leonardo Bassan, Gabriel Dessotti Barretto, Felipe Campos de Almeida, Patricia Vianna Bonini Palma, Larissa Sarri Binelli, Joao Paulo Lettieri da Silva, Caroline Fontanari, Ricardo Cardoso Castro, Lorena Lobo de Figueiredo Pontes, Fabiani Gai Frantz, Fabiola Attie de Castro
Summary: Philadelphia-negative myeloproliferative neoplasms (MPN) are hematological diseases associated with driver mutations in JAK2, CALR, and MPL genes. Chronic inflammation and alterations in stromal and immune cells may contribute to the pathophysiology of MPN. The frequency and immunophenotype of peripheral blood monocyte subpopulations were evaluated in patients with MPN, showing alterations in monocyte subpopulations frequency and surface markers expression pattern, which may be associated with MPN pathophysiology.
MEDICAL ONCOLOGY (2022)
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Article Agriculture, Dairy & Animal Science
MHCII Expression on Peripheral Blood Monocytes in Canine Lymphoma: An Impact of Glucocorticoids
Alicja Rzepecka, Dariusz Jagielski, Anna Cywinska, Rafal Sapierzynski, Magdalena Zmigrodzka, Olga Witkowska-Pilaszewicz, Anna Winnicka
Summary: This study evaluated the changes in MHCII expression in monocytes of dogs with lymphoma, and found an increase in the percentage of MHCII- monocytes regardless of treatment. However, only in dogs that had received glucocorticoids, changes in the proportion of MHCII+ and MHCII- monocytes were reflected by the changes in the number of MHCII- monocytes in the blood, which was significantly higher. These results suggest that evaluating MHCII expression changes in monocytes could be helpful in diagnosing lymphoma, monitoring treatment, or assessing immune status in dogs.
ANIMALS (2022)
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Article Medicine, Research & Experimental
Immunophenotypic changes of monocytes in myelodysplastic syndrome and clinical significance
Lijuan Li, Shunjie Yu, Xian Hu, Zhaoyun Liu, Xiaoying Tian, Xiaotong Ren, Xinyu Guo, Rong Fu
Summary: This study utilizes immunophenotypic analysis to uncover the abnormalities in differentiation and maturation of monocytes in patients with Myelodysplastic syndrome (MDS). It reveals the significant association between CD300e expression and disease progression. These findings provide important insights into the diagnosis, differentiation, and prognosis of MDS.
CLINICAL AND EXPERIMENTAL MEDICINE (2023)
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Article Cardiac & Cardiovascular Systems
Immune Profiling Reveals Decreases in Circulating Regulatory and Exhausted T Cells in Human Hypertension
Matthew R. Alexander, Bethany L. Dale, Charles D. Smart, Fernando Elijovich, Cara E. Wogsland, Sierra M. Lima, Jonathan M. Irish, Meena S. Madhur
Summary: Evidence from nonhuman animal models suggests that immune cells play a crucial role in hypertension, but their changes in human hypertension are unclear. Using mass cytometry, this study reveals reduced levels of CCR10+ regulatory T cells (Tregs) and PD-1+CD57-CD8+ memory T cells, indicating potential decreases in anti-inflammatory and hypofunctional T-cell populations in human hypertension.
JACC-BASIC TO TRANSLATIONAL SCIENCE (2023)
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Article Clinical Neurology
Predicting neurological recovery after traumatic spinal cord injury by time-resolved analysis of monocyte subsets
Raban Arved Heller, Julian Seelig, Helena Lucia Crowell, Maximilian Pilz, Patrick Haubruck, Qian Sun, Lutz Schomburg, Volker Daniel, Arash Moghaddam, Bahram Biglari
Summary: This study aimed to evaluate the correlation between remission after traumatic spinal cord injury and the dynamics of monocyte subsets, lymphocytes' responsive potential, cytokine expression, patterns of trace element concentration, and clinical covariates. Clinical research findings suggest that early dynamics in monocyte subsets can predict recovery from traumatic spinal cord injury.
BRAIN (2021)
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Article Immunology
Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines
Patrick P. G. Mulder, Marcel Vlig, Esther Fasse, Matthea M. Stoop, Anouk Pijpe, Paul P. M. van Zuijlen, Irma Joosten, Bouke K. H. L. Boekema, Hans J. P. M. Koenen
Summary: The immune response in burn patients is often extreme and abnormal. Understanding the immune effects of thermal injury is necessary to improve patient outcomes. This study shows that after burn injury, immune cells persistently increase in number, unlike in normal wound healing. The study also reveals high levels of chemokines and pro-inflammatory cytokines in burn tissue. The local immune response in burns is similar to the systemic immune reaction, but differs in neutrophil maturity and lymphocyte composition.
FRONTIERS IN IMMUNOLOGY (2022)
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Article Multidisciplinary Sciences
Stroke induces disease-specific myeloid cells in the brain parenchyma and pia
Carolin Beuker, David Schafflick, Jan-Kolja Strecker, Michael Heming, Xiaolin Li, Jolien Wolbert, Antje Schmidt-Pogoda, Christian Thomas, Tanja Kuhlmann, Irene Aranda-Pardos, Noelia A-Gonzalez, Praveen Ashok Kumar, Yves Werner, Ertugrul Kilic, Dirk M. Hermann, Heinz Wiendl, Ralf Stumm, Gerd Meyer zu ho*rste, Jens Minnerup
Summary: The authors of this study found a stroke-associated myeloid cell population in the brain parenchyma that shares similarities with neurodegenerative microglia. These cells, primarily derived from resident microglia, exhibit a lipid-phagocytosing phenotype. Blocking specific markers on these cells can partially improve stroke outcomes.
NATURE COMMUNICATIONS (2022)
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Article Endocrinology & Metabolism
S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction
Sagarika Chakrabarty, Quyen Bui, Leylla Badeanlou, Kelly Hester, Jerold Chun, Wolfram Ruf, Theodore P. Ciaraldi, Fahumiya Samad
Summary: Sphingosine-1-phosphate (SIP) plays an important role in regulating cell growth, immune cell trafficking, and inflammation. Increased expression of S1PR3 in adipose tissues and the liver is associated with obesity and metabolic dysfunction. S1P-S1PR3 signaling pathway defends against excessive inflammation and steatosis in adipose and liver to maintain metabolic homeostasis.
ADIPOCYTE (2022)
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Article Cardiac & Cardiovascular Systems
Rationale and design of a study to assess the safety and efficacy of rNAPc2 in COVID-19: the Phase 2b ASPEN-COVID-19 trial
Connie N. Hess, Warren H. Capell, Michael R. Bristow, Wolfram Ruf, Michael Szarek, David A. Morrow, Jose C. Nicolau, Christopher A. Graybill, Debra Marshall, Judith Hsia, Marc P. Bonaca
Summary: The ASPEN-COVID-19 study aims to evaluate a novel therapeutic approach for COVID-19 by targeting tissue factor. The study design includes a randomized phase 2b trial with 160 participants and focuses on D-dimer levels and bleeding events as primary endpoints.
AMERICAN HEART JOURNAL (2022)
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Letter Oncology
Authors' reply to the Letter to the Editor: Tissue factor and its procoagulant activity on cancer-associated thromboembolism in pancreatic cancer
Shiro Koizume, Satoshi Kobayashi, Wolfram Ruf, Yohei Miyagi
Summary: Tissue factor-procoagulant activity on cells is regulated by multiple molecular mechanisms. Patients with a high tissue factor antigen level are at a higher risk for cancer-associated thromboembolism. The use of validated ELISA methods, such as the Quantikine assay, can contribute to more precise prediction of this condition.
CANCER SCIENCE (2022)
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Review Hematology
Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy
Alan E. Mast, Wolfram Ruf
Summary: Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein that inhibits the initiation phase of coagulation. TFPI acts at cells expressing tissue factor (TF) and at sites of injury, regulating bleeding in hemophilia. It has different isoforms that inhibit factor Xa and TF-FVIIa, and by forming complexes with cellular receptors, TFPI alters cellular trafficking and signaling pathways. Antibodies to TFPI's Kunitz 2 domain can effectively block thrombin generation in vessel injury and be used in hemophilia treatment.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2022)
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Article Cardiac & Cardiovascular Systems
Aircraft noise exposure induces pro-inflammatory vascular conditioning and amplifies vascular dysfunction and impairment of cardiac function after myocardial infarction
Michael Molitor, Maria T. Bayo-Jimenez, Omar Hahad, Claudius Witzler, Stefanie Finger, Venkata S. Garlapati, Sanela Rajlic, Tanja Knopp, Tabea K. Bieler, Melania Aluia, Johannes Wild, Jeremy Lagrange, Recha Blessing, Steffen Rapp, Andreas Schulz, Hartmut Kleinert, Susanne Karbach, Sebastian Steven, Wolfram Ruf, Philipp Wild, Andreas Daiber, Thomas Muenzel, Philip Wenzel
Summary: The study found that aircraft noise may have a significant impact on the development and deterioration of ischaemic heart disease. Exposure to noise before myocardial infarction (MI) can induce cardiovascular dysfunction and inflammation, leading to worsened cardiac function and increased inflammation in the vascular and cardiac tissues. The findings suggest that reducing environmental noise exposure may improve the clinical outcomes of patients with MI.
CARDIOVASCULAR RESEARCH (2023)
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Letter Dermatology
DKK3 Promotes Oxidative Stress-Induced Fibroblast Activity
Sabrina Muecklich, Khuram Shehzad, Jessica Tiemann, Li Li, Sonja Leson, Peter J. Nelson, Richard Jennemann, Matthias Klein, Christian Becker, Roger Sandhoff, Kerstin Steinbrink, Verena K. Raker
JOURNAL OF INVESTIGATIVE DERMATOLOGY (2023)
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Article Hematology
Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis
Asim Cengiz Akbulut, Ryanne A. Arisz, Constance C. F. M. J. Baaten, Gaukhar Baidildinova, Aarazo Barakzie, Rupert Bauersachs, Jur Ten Berg, Wout W. A. van den Broek, H. C. de Boer, Amandine Bonifay, Vanessa Broker, Richard J. Buka, Hugo ten Cate, Arina J. ten Cate-Hoek, S. Cointe, Ciro De Luca, Ilaria De Simone, Rocio Vacik Diaz, Francoise Dignat-George, Kathleen Freson, Giulia Gazzaniga, Eric C. M. van Gorp, Anxhela Habibi, Yvonne M. C. Henskens, Aaron F. J. Iding, Abdullah Khan, Gijsje H. Koenderink, Akhil Konkoth, Romaric Lacroix, Trisha Lahiri, Wilbur Lam, Rachel E. Lamerton, Roberto Lorusso, Qi Luo, Coen Maas, Owen J. T. McCarty, Paola E. J. van der Meijden, Joost C. M. Meijers, Adarsh K. Mohapatra, Neta Nevo, Alejandro Pallares Robles, Philippe Poncelet, Christoph Reinhardt, Wolfram Ruf, Ronald Saraswat, Claudia Schonichen, Roger Schutgens, Paolo Simioni, Stefano Spada, Henri M. H. Spronk, Karlygash Tazhibayeva, Jecko Thachil, Rocio Vacik Diaz, L. Vallier, Alicia Veninga, Peter Verhamme, Chantal Visser, Steve P. Watson, Philip Wenzel, Ruth A. L. Willems, Anne Willers, Pengyu Zhang, Konstantinos Zifkos, Anton Jan van Zonneveld
Summary: The Fourth Maastricht Consensus Conference on Thrombosis covered a wide range of topics, including the role of coagulation proteins in cardiovascular disease, novel mechanisms of thrombosis, strategies to limit bleeding risks, hemostasis in extracorporeal systems, and clinical dilemmas in thrombosis and antithrombotic management. The conference also revisited the coagulopathy associated with COVID-19.
THROMBOSIS AND HAEMOSTASIS (2023)
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Article Multidisciplinary Sciences
Deletion of endothelial leptin receptors in mice promotes diet-induced obesity
Rajinikanth Gogiraju, Claudius Witzler, Fatemeh Shahneh, Astrid Hubert, Luisa Renner, Magdalena L. Bochenek, Konstantinos Zifkos, Christian Becker, Madhusudhan Thati, Katrin Schaefer
Summary: Obesity promotes endothelial dysfunction, and endothelial cells may actively contribute to the development of obesity and metabolic dysfunction. This study reveals the important role of endothelial leptin receptors in the transport of leptin into the brain and neuronal control of food intake, suggesting organ-specific changes in endothelial cell metabolism.
SCIENTIFIC REPORTS (2023)
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Article Gastroenterology & Hepatology
Crohn's disease proteolytic microbiota enhances inflammation through PAR2 pathway in gnotobiotic mice
Alba Santiago, Amber Hann, Marco Constante, Sara Rahmani, Josie Libertucci, Kyle Jackson, Gaston Rueda, Laura Rossi, Ramachandran Rithwick, Wolfram Ruf, Jon Schertzer, Alberto Caminero, Premysl Bercik, Heather Jean Galipeau, Elena Francisca Verdu
Summary: Emerging evidence suggests that microbial proteolytic activity is implicated in ulcerative colitis (UC), but its role in Crohn's disease (CD) remains unclear. This study investigated the effects of colonizing germ-free mice with CD microbiota and healthy control microbiota. It was found that CD proteolytic microbiota increased colitis severity through a PAR2 pathway. These findings highlight the proinflammatory nature of CD proteolytic microbiota and its role in exacerbating colitis.
GUT MICROBES (2023)
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Article Hematology
Tumor-expressed factor VII is associated with survival and regulates tumor progression in breast cancer
Chantal Kroone, Chris Tieken, Beguem Kocaturk, Madelon Paauwe, Erik J. Blok, Betuel Unlu, Yascha W. van den Berg, Eliana Stanganello, Maaike Y. Kapteijn, Nathalie Swier, Xi Zhang, Danique E. M. Duits, Yazhi Lin, Lisa V. E. Oostenbrink, Rob F. P. van den Akker, Laurent O. Mosnier, Lukas J. Hawinkels, Bart J. M. van Vlijmen, Wolfram Ruf, Peter J. Kuppen, Suzanne C. Cannegieter, Jeroen T. Buijs, Henri H. Versteeg
Summary: Cancer enhances the risk of venous thromboembolism and promotes cancer progression by creating a hypercoagulant microenvironment. Although anticoagulants have been considered as a potential anticancer treatment, their effect on cancer progression remains unclear. The study reveals that breast cancer cells express increased levels of factor VII (FVII), which stimulates epithelial-to-mesenchymal transition (EMT) and metastasis. Surprisingly, liver-derived FVII inhibits metastasis. It suggests that tumor-expressed FVII and liver-derived FVII have opposing effects on EMT and metastasis.
BLOOD ADVANCES (2023)
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Article Hematology
Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial
Connie N. Hess, Judith Hsia, Ian A. Carroll, Mark R. Nehler, Wolfram Ruf, David A. Morrow, Jose C. Nicolau, Otavio Berwanger, Michael Szarek, Warren H. Capell, Shilpa Johri, Michael S. Pursley, Ryan Gupta, Patrick S. Meehan, Francesco Franchi, Mark B. Effron, Debra Marshall, Christopher A. Graybill, Sophia P. Huebler, Thomas Keuer, Michael R. Bristow, Marc P. Bonaca
Summary: Thrombo-inflammation plays a central role in COVID-19-associated coagulopathy. The novel TF inhibitor rNAPc2 may be a potential therapeutic target for COVID-19, however, its safety and efficacy are still unknown.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY (2023)
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Article Endocrinology & Metabolism
Commensal bacteria weaken the intestinal barrier by suppressing epithelial neuropilin-1 and Hedgehog signaling
Giulia Pontarollo, Bettina Kollar, Amrit Mann, My Phung Khuu, Klytaimnistra Kiouptsi, Franziska Bayer, Ines Brandao, Valeriya V. V. Zinina, Jennifer Hahlbrock, Frano Malinarich, Maximilian Mimmler, Sudhanshu Bhushan, Federico Marini, Wolfram Ruf, Meriem Belheouane, John F. F. Baines, Kristina Endres, Scott M. M. Reba, Verena K. K. Raker, Carsten Deppermann, Christoph Welsch, Markus Bosmann, Natalia Soshnikova, Benoit Chassaing, Mattias Bergentall, Felix Sommer, Fredrik Backhed, Christoph Reinhardt
Summary: The gut microbiota weakens the intestinal barrier by suppressing epithelial neuropilin-1 (NRP1) and Hedgehog (Hh) signaling. Activation of Toll-like receptor-2 (TLR2) by commensal microbiota dampens Hh pathway signaling, resulting in decreased NRP1 protein levels. Conversely, elevated NRP1 levels in germ-free mice are associated with a strengthened gut barrier.
NATURE METABOLISM (2023)
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Article Medicine, Research & Experimental
Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure
Venkata Garlapati, Michael Molitor, Thomas Michna, Gregory S. Harms, Stefanie Finger, Rebecca Jung, Jeremy Lagrange, Panagiotis Efentakis, Johannes Wild, Maike Knorr, Susanne Karbach, Sabine Wild, Ksenija Vujacic-Mirski, Thomas Muenzel, Andreas Daiber, Moritz Brandt, Tommaso Gori, Hendrik Milting, Stefan Tenzer, Wolfram Ruf, Philip Wenzel
Summary: Despite advances in MI interventions, adverse cardiac remodeling and fibrosis leading to IHF remain a major cause of death. A profibrotic coagulation signaling pathway involving MAPK could be targeted for improved cardiac function post-MI. Targeted interventions with trametinib in this pathway show promising results in a murine model.
JOURNAL OF CLINICAL INVESTIGATION (2023)
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