Article
Biochemistry & Molecular Biology
Shuoqi Zhang, Yuze Cao, Jingwen Du, Huan Liu, Xiaojing Chen, Mengdi Li, Mengqi Xiang, Chengyue Wang, Xiaoming Wu, Langjiao Liu, Chunli Wang, Yinsong Wu, Zhuxin Li, Shaohong Fang, Jialan Shi, Lihua Wang
Summary: This study explored the role of circulating neutrophil extracellular traps (NETs) in tissue plasminogen activator (t-PA) resistance in acute ischemic stroke patients. The NETs were found to activate platelets and endothelial cells, affecting the coagulation and fibrinolysis process. Targeting NETs may be a promising therapeutic approach to enhance the efficacy of t-PA thrombolysis in AIS patients.
Review
Clinical Neurology
Precious Jolugbo, Robert A. S. Ariens
Summary: Thrombi in stroke are highly heterogeneous, consisting of fibrin, platelets, red blood cells, VWF, and neutrophil extracellular traps. These thrombi can be roughly divided into fibrin-rich and red blood cell-rich clots. Fibrin-rich clots are associated with increased recanalization maneuvers, longer procedure times, and less favorable clinical outcomes compared with red blood cell-rich clots.
Article
Hematology
Ji-He Li, Dong-Xia Tong, Ying Wang, Lei Gao, Yue Liu, Xiao-Hui Zhang, Wen-Jia Chen, Jin-Yv Chi, Na Liu, Kelaier Yang, Shi-Peng Wang, Yang Xu, Yang Li, Xin-Hua Yin, Wen-Xiu Liu
Summary: Patients with essential hypertension and hyperhomocysteinemia have higher levels of neutrophil extracellular trap (NET) release, which is positively correlated with homocysteine levels, neutrophil-lymphocyte ratio (NLR), and hypercoagulable markers. This leads to a more hypercoagulable state in these patients, suggesting that blocking NETs may be a new therapeutic target for preventing thrombosis.
THROMBOSIS RESEARCH
(2021)
Review
Oncology
Hao Zhang, Yanghanzhao Wang, Mengdi Qu, Wenqian Li, Dan Wu, Juan P. P. Cata, Changhong Miao
Summary: Sepsis is a life-threatening condition characterized by dysfunction of the immune system and multiple organ failure due to exaggerated response to infection. Endothelial dysfunction is a hallmark of sepsis. Excessive neutrophil activation and release of neutrophil extracellular traps (NETs) contribute to endothelial cell pro-inflammatory and pro-coagulant phenotype, leading to compromised microcirculation, tissue hypoperfusion, and organ failure.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Hematology
Kathryn E. Hally, Olivia M. Parker, Morgane M. Brunton-O'Sullivan, Scott A. Harding, Peter D. Larsen
Summary: Combining biomarkers of NETosis and platelet activation is important for predicting MACE in patients with AMI. Composite biomarker scores, inclusive of both NETosis and platelet activation biomarkers, were independent predictors of 1-year MACE, showing a stronger association when combined.
THROMBOSIS AND HAEMOSTASIS
(2021)
Review
Immunology
Zhaoyuan Chen, Hao Zhang, Mengdi Qu, Ke Nan, Hanzhong Cao, Juan P. Cata, Wankun Chen, Changhong Miao
Summary: Patients with sepsis often have coagulation dysfunction and the formation of thrombus, with neutrophil extracellular traps (NETs) playing a key role in sepsis. Clinical evaluation of NETs function could be a valuable biomarker for early diagnosis of sepsis. The interaction of NETs with platelets, complement, and endothelium mediates the formation of immunothrombosis in sepsis, and inhibiting NETs formation is considered a potential treatment for sepsis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maria Amparo Blanch-Ruiz, Raquel Ortega-Luna, Maria Angeles Martinez-Cuesta, Angeles Alvarez
Summary: Cardiovascular diseases are a leading cause of death, with blood-cell interactions and endothelial dysfunction playing a key role in thrombus formation. Neutrophil extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) have been reported to contribute to thrombosis through various mechanisms, requiring exhaustive analysis of their structure and composition to clarify their role in pathological thrombus formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
In Soo Kim, Do Hyun Kim, Hoi Woul Lee, Sung Gyun Kim, Yong Kyun Kim, Jwa-Kyung Kim
Summary: This study found a strong association between elevated neutrophil extracellular trap (NET) levels and poor clinical outcomes in patients with COVID-19. The role of NETs in COVID-19-associated acute kidney injury (AKI) was also investigated. The results showed that elevated NET levels were closely associated with AKI and were a significant predictor of mortality in COVID-19 patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Somanathapura K. NaveenKumar, Mahadevappa Hemshekhar, Bidare N. Sharathbabu, Kempaiah Kemparaju, Govindasamy Mugesh, Kesturu S. Girish
Summary: Cell-free heme (CFH) is a product of hemoglobin, myoglobin, and hemoprotein degradation and plays a key role in the progression of lung disease pathology. Heme-induced platelet activation and ferroptosis lead to neutrophil aggregation and NET formation, causing pulmonary damage. Redox modulators and ferroptosis inhibitors may be potential therapies for respiratory distress-associated complications.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Immunology
Ann-Katrin Wienkamp, Luise Erpenbeck, Jan Rossaint
Summary: Platelets play a crucial role in hemostasis and also participate in host innate immunity, sensing bacterial products and releasing microbicidal proteins and chemokines. They interact with neutrophils to form neutrophil extracellular traps (NETs) and contribute to immunothrombosis. In COVID-19 patients, NETs are associated with thrombosis and increased mortality.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Alexander A. Fields, Elizabeth Andraska, Christof A. Kaltenmeier, Zachary Matthay, Kimberly Herrera, Brenda M. Nunez-Garcia, Chayse D. Jones, Katherine Wick, Silvia Liu, Jian-Hua Luo, Yan-Ping A. Yu, Michael M. Matthay, Carolyn J. Hendrickson, Roland J. Bainton, Tessa S. Barrett, Jeffrey D. Berger, Matthew Z. Neal, Lucy Kornblith
Summary: This study found that plasma from COVID-19 patients can induce abnormal platelet function and promote inflammatory response in neutrophils. The soluble components in plasma had an impact on the behavior of platelets and neutrophils, which may contribute to the thromboinflammatory complications observed in COVID-19.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Maximilian Ackermann, Hans-Joachim Anders, Rostyslav Bilyy, Gary L. Bowlin, Christoph Daniel, Rebecca De Lorenzo, Mikala Egeblad, Timo Henneck, Andres Hidalgo, Markus Hoffmann, Bettina Hohberger, Yogendra Kanthi, Mariana J. Kaplan, Jason S. Knight, Jasmin Knopf, Elzbieta Kolaczkowska, Paul Kubes, Moritz Leppkes, Aparna Mahajan, Angelo A. Manfredi, Christian Maueroeder, Norma Maugeri, Ioannis Mitroulis, Luis E. Munoz, Teluguakula Narasaraju, Elisabeth Naschberger, Indira Neeli, Lai Guan Ng, Marko Z. Radic, Konstantinos Ritis, Patrizia Rovere-Querini, Mirco Schapher, Christine Schauer, Hans-Uwe Simon, Jeeshan Singh, Panagiotis Skendros, Konstantin Stark, Michael Stuerzl, Johan van der Vlag, Peter Vandenabeele, Ljubomir Vitkov, Maren von Koeckritz-Blickwede, Cansu Yanginlar, Shida Yousefi, Alexander Zarbock, Georg Schett, Martin Herrmann
Summary: SARS-CoV-2 infection poses a major threat to multiple organs, with severe cases showing dysregulated immune responses. The imbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of severe COVID-19 cases. Therapeutic strategies targeting dysregulated NET formation or degradation may benefit severe COVID-19 patients.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Hematology
Agostina Carestia, Laura C. Godin, Craig N. Jenne
Summary: Platelets play a crucial role in immunity and coagulation, able to detect, interact with, and kill pathogens. They induce the formation of microthrombi to prevent pathogen spread and facilitate clearance in the process of immunothrombosis.
THROMBOSIS RESEARCH
(2023)
Article
Immunology
Xuanqi Liu, Yinping Huo, Jingyang Zhao, Guan Wang, Huiyang Liu, Fangrui Yin, Chunyan Pang, Yongfu Wang, Li Bai
Summary: The endothelial cell protein C receptor (EPCR) plays a crucial role in rheumatoid arthritis (RA) by affecting the disease progression and function of polymorphonuclear neutrophils (PMN). PMN cells with low EPCR expression migrate into the joint cavity and contribute to RA synovial inflammation, leading to bone destruction. The formation of PMN-neutrophil extracellular traps (NETs) in RA patients is increased, which can be regulated by the APC-EPCR signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Hematology
Carmelo Gurnari, Massimo Breccia, Francesca Di Giuliano, Emilia Scalzulli, Mariadomenica Divona, Alfonso Piciocchi, Laura Cicconi, Eleonora De Bellis, Adriano Venditti, Maria Ilaria Del Principe, William Arcese, Francesco Lo-Coco, Francesco Garaci, Maria Teresa Voso
Summary: Patients with acute promyelocytic leukaemia (APL) who experience intracranial haemorrhage (ICH) are typically older and more likely to have high-risk APL. Positivity for the 'swirl' sign and hydrocephalus on neuroradiological imaging are predictors of a fatal outcome.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Nan Zuo, Wenhui Liu, Tenglong Hu, Yingmiao Liu, Baorong Li, Huan Liu, Haijiao Jing, Xiaojing Chen, Yueyue Li, Jingwen Du, Tianshui Hu, Zengxiang Dong, Yumei Niu, Jialan Shi
Summary: The prothrombotic state in patients with periodontitis is mediated by PS+ cells and microvesicles stimulated by elevated levels of inflammatory cytokines. PS exposure on blood cells and endothelial cells significantly decreased after inhibiting the effect of inflammatory cytokines. Non-surgical periodontal therapy significantly attenuated the release of microvesicles and the PS exposure of blood cells in severe periodontitis.
JOURNAL OF PERIODONTOLOGY
(2022)
Article
Cell Biology
Yiming Feng, Yue Zhang, Jialan Shi
Summary: Classical myeloproliferative neoplasm (MPN) is a clonal disease characterized by abnormal expansion of hematopoietic stem cells. MPN patients are more susceptible to thrombotic events, but antiplatelet therapies may cause bleeding. Platelets play a critical role in the pathogenesis of MPN and optimizing antithrombotic treatment strategies by adjusting the administration of antiplatelet drugs may achieve simultaneous control of thrombosis and bleeding.
Review
Cell Biology
Chengyue Wang, Chengyuan Yu, Valerie A. Novakovic, Rujuan Xie, Jialan Shi
Summary: As more is learned about the pathophysiological mechanisms of COVID-19, systemic thrombosis has been recognized as being associated with more severe clinical manifestations, mortality and sequelae. Microparticles (MPs) are membrane bubbles released in response to activation, injury or apoptosis of cells, and can be used as a risk factor to predict renal microthrombosis and kidney injury. Early prophylactic anticoagulant therapy reduces mortality and improves clinical outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Haijiao Jing, Nan Zuo, Valerie A. Novakovic, Jialan Shi
Summary: Cancer patients are more susceptible to SARS-CoV-2 and may develop severe COVID-19 infections. Approximately 20% of COVID-19 patients with cancer experience venous thrombosis. Thrombus formation is associated with severe clinical manifestations, mortality, and sequelae. This review focuses on the pathophysiological mechanisms of thrombosis in COVID-19 patients with cancer and proposes an antithrombotic strategy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Immunology
Chengyue Wang, Chengyuan Yu, Haijiao Jing, Xiaoming Wu, Valerie A. Novakovic, Rujuan Xie, Jialan Shi
Summary: Many discharged COVID-19 patients with sequelae suffer from reduced quality of life, which places a burden on the healthcare system, families, and society. The pathophysiological mechanisms of long COVID involve persistent viral replication, chronic hypoxia, and inflammation. Thrombosis plays a crucial role in the impairment of various organ functions. Currently, there is no effective treatment for long COVID. However, there is growing evidence that early anticoagulation therapy can improve outcomes by reducing thrombotic sequelae.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Hematology
Christopher Carman, Dessislava N. Nikova, Yumiko Sakurai, Jialan Shi, Valerie A. Novakovic, Jan T. Rasmussen, Wilbur A. Lam, Gary E. Gilbert
Summary: Prior reports have indicated that convex membrane curvature of phosphatidylserine (PS)-containing vesicles enhances the formation of binding sites for factor Va and lactadherin, but the relationship between convex curvature and protein localization on cells remains unknown. In this study, a membrane topology model was developed to explore this relationship further. Results show that the ridges of membranes with maximal curvature selectively bound lactadherin and factor Va, supporting the assembly of prothrombinase complexes.
Review
Cardiac & Cardiovascular Systems
Langjiao Liu, Haijiao Jing, Xiaoming Wu, Mengqi Xiang, Valerie A. Novakovic, Shuye Wang, Jialan Shi
Summary: This article describes the pathophysiological mechanism by which SARS-CoV-2 induces lung and heart complications through injury of endothelial cells, emphasizing the procoagulant effect of microparticles (MPs) and phosphatidylserine (PS), and demonstrates the importance of early antithrombotic therapy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Immunology
Mengqi Xiang, Xiaoming Wu, Haijiao Jing, Langjiao Liu, Chunxu Wang, Yufeng Wang, Valerie A. A. Novakovic, Jialan Shi
Summary: Patients with COVID-19 often experience hypoxemia, impaired lung function, and abnormal imaging manifestations. Platelet activation and abnormalities contribute to increased pulmonary permeability, gas exchange disorders, and an increased risk of thrombotic events. Phosphatidylserine (PS) plays a significant role in thrombus formation. Antiplatelet therapy and targeting PS may be potential treatment strategies for COVID-19 hypercoagulability and thrombosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Infectious Diseases
Xiaoming Wu, Mengqi Xiang, Haijiao Jing, Langjiao Liu, Chunli Wang, Valerie A. Novakovic, Jialan Shi
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Review
Immunology
Haijiao Jing, Xiaoming Wu, Mengqi Xiang, Langjiao Liu, Valerie A. Novakovic, Jialan Shi
Summary: This review investigates the crosstalk between inflammation and thrombosis in COVID-19 patients, focusing on the contributions of inflammation to thrombosis pathogenesis and proposing combined use of anti-inflammatory and anticoagulant therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Peripheral Vascular Disease
Xiaoming Wu, Mengqi Xiang, Haijiao Jing, Chengyue Wang, Valerie A. Novakovic, Jialan Shi
Summary: The emergence of viral variants has resulted in the ongoing global battle against COVID-19, while a subset of convalescent individuals continues to experience persistent and prolonged sequelae known as long COVID. Various studies demonstrate endothelial injury in acute COVID-19 and convalescent patients, highlighting its central role in the progression of COVID-19 and development of long COVID. Different organs possess different types of endothelia with specific features, forming distinct endothelial barriers and executing diverse physiological functions. Endothelial injury leads to increased permeability, glycocalyx shedding, extension of phosphatidylserine-rich filopods, and barrier damage. This article primarily focuses on these endothelial barriers and their contribution to long COVID.
Article
Gastroenterology & Hepatology
Subodh Kumar, Jiangning Zhao, Srikanth Talluri, Leutz Buon, Shida Mu, Lakshmi B. Potluri, Chengcheng Liao, Jialan Shi, Chandraditya Chakraborty, Gabriel B. Gonzalez, Yu-Tzu Tai, Jaymin Patel, Jagannath Pal, Hiroshi Mashimo, Mehmet K. Samur, Nikhil C. Munshi, Masood A. Shammas
Summary: This study identified APE1 as a driver of genomic evolution in esophageal adeno-carcinoma and other solid tumors. APE1 suppression caused cell cycle arrest, impaired growth, and increased cell toxicity, while APE1 overexpression led to massive chromosomal instability and oncogenic transformation. Inhibitors targeting APE1 have the potential to treat EAC and other cancers by regulating genomic instability.
Review
Oncology
Haijiao Jing, Xiaoming Wu, Mengqi Xiang, Chengyue Wang, Valerie A. Novakovic, Jialan Shi
Summary: Tumor progression and metastasis are associated with the release of microparticles (MPs) that contain phosphatidylserine (PS) and nucleic acids. Coagulation factors and platelets play important roles in promoting tumor development, angiogenesis, and metastasis. Anticoagulation therapy targeting the phosphatidylserine-mediated coagulation cascade can slow tumor progression and improve patient treatment. Development of therapies targeting platelet activation and platelet-tumor cell interactions may also impede tumor growth and spread.
Review
Cardiac & Cardiovascular Systems
Mengqi Xiang, Xiaoming Wu, Haijiao Jing, Valerie A. Novakovic, Jialan Shi
Summary: The role of hypoxia, vascular endothelial injury, and thrombotic inflammation in worsening COVID-19 symptoms has been widely recognized. Obesity is an independent risk factor for severe respiratory diseases and can aggravate the acute phase of COVID-19. Early interventions, such as supplemental oxygen and comprehensive antithrombotic therapy, are recommended to reduce ICU admissions, mortality, and sequelae.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Oncology
Chengcheng Liao, Srikanth Talluri, Jiangning Zhao, Shidai Mu, Subodh Kumar, Jialan Shi, Leutz Buon, Nikhil C. Munshi, Masood A. Shammas
Summary: This study shows that increased expression of RAD51 is associated with poor prognosis in esophageal, breast, and colon cancer patients. Elevated RAD51 promotes growth and contributes to spontaneous and chemotherapy-induced damage and instability of genetic material in cancer cells. RAD51 inhibitors can prevent the activation of these mechanisms, inhibiting the growth of cancer cells while preserving the integrity of genetic material and the immune system.