Article
Hematology
S. N. Tchaikovski, M. C. L. G. D. Thomassen, E. Stickeler, K. Bremme, J. Rosing
Summary: This study found that women with previous hormone-related thrombosis exhibited higher thrombin generation, APC resistance, and protein S/TFPI ratios at low TF conditions. Smoking decreased thrombin generation under assay conditions and affected the function of the TFPI system.
THROMBOSIS RESEARCH
(2021)
Article
Hematology
Xiuri Jin, Sachiko Kinoshita, Hiroyuki Kuma, Tomohide Tsuda, Tatsusada Yoshida, Dongchon Kang, Naotaka Hamasaki
Summary: Measuring protein S-specific activity can rapidly identify carriers of abnormal protein S molecules, helping in predicting and preventing venous thrombosis.
CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
(2021)
Article
Hematology
Xian Li, Xiaohong Song, Dlovan F. D. Mahmood, Martha M. S. Sim, Sara J. Bidarian, Jeremy P. Wood
Summary: TFPIα and APC exhibit stronger anticoagulant activity when combined with PS, while antibodies against TFPI and APC have an additive procoagulant effect. In purified protein systems, TFPIα dose-dependently inhibits thrombin activation by prothrombinase only in the presence of APC, and this activity is enhanced by PS. Platelets protect prothrombinase from inhibition, maintaining a procoagulant environment within the clot.
THROMBOSIS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Janina Wittig, Maria-Kyriaki Drekolia, Anastasia Kyselova, Fredy Delgado Lagos, Magdalena L. Bochenek, Jiong Hu, Katrin Schaefer, Ingrid Fleming, Sofia-Iris Bibli
Summary: This study investigated the impact of endothelial cell-driven oxidative post-translational modifications on the activity of TFPI. The researchers found that S-sulfhydration modification can affect the interaction between TFPI and factor Xa, thereby facilitating the activation of tissue factor. Loss of endothelial CSE expression/activity reduces the S-sulfhydration modification of TFPI. The study also found that S-sulfhydration modification of TFPI regulates blood coagulation.
Article
Hematology
Adrienn Teraz-Orosz, Magdalena Gierula, Anastasis Petri, David Jones, Renos Keniyopoullos, Patricia Badia Folgado, Salvatore Santamaria, James T. B. Crawley, David A. Lane, Josefin Ahnstrom
Summary: Protein S is a cofactor that enhances the inhibition of factor XIII activity and generation by TFPI alpha. The interaction between TFPI alpha and protein S is critical for this enhancement, and binding of C4BP to protein S LG1 abolishes the TFPI cofactor function. The amino acids involved in TFPI alpha enhancement and the mechanisms behind the reduced TFPI cofactor function of C4BP-bound protein S were investigated. It was found that Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 of protein S are critical for its function, and binding of the C4BP beta-chain blocks this function.
Article
Biology
Lu Yin, Yuan Qi, Zhiru Ge, Jiajin Li
Summary: This study examined the effects of dabigatran and rivaroxaban on the activities of coagulation factors. The results showed that low doses of dabigatran inhibited activated protein C (APC) activity, while high doses of dabigatran and rivaroxaban inhibited the activities of several coagulation factors, with a more significant effect at higher drug concentrations.
OPEN LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ankita Arora, Roberto Castro-Gutierrez, Charlie Moffatt, Davide Eletto, Raquel Becker, Maya Brown, Andreas E. Moor, Holger A. Russ, J. Matthew Taliaferro
Summary: The study reveals that there are numerous RNAs enriched in the projections of neuronal cells, and identifies sequence elements that regulate their localization. These localization elements are enriched in adenosine and guanosine residues, and are tens to hundreds of nucleotides long. The RNA-binding protein Unk is associated with these localization elements and is functionally required for RNA trafficking to neurites.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Susan J. Keam
Summary: Concizumab is a subcutaneously administered humanised monoclonal IgG4 antibody developed by Novo Nordisk for the treatment of hemophilia A and B. It binds to the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI) and prevents TFPI from binding to activated Factor X. In March 2023, it was approved in Canada for the treatment of adolescent and adult patients with hemophilia B who have FIX inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
Article
Hematology
Amy E. Siebert, Susan A. Maroney, Nicholas D. Martinez, Alan E. Mast
Summary: The study focused on investigating the biological activities of platelet TFPI alpha (pTFPI alpha) by characterizing the effects of pTFPI alpha overexpression in Tfpi(-/-) mice. Results showed that pTFPI alpha overexpression rescued Tfpi(-/-) embryos from mid-gestational lethality but did not affect late gestational cerebrovascular defects. The study also identified strain-specific genetic interactions modulating Tfpi(-/-) embryonic survival and emphasized the importance of meticulously characterizing transgenic mouse models to avoid misinterpretation of results.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Review
Immunology
Omid Teymournejad, Christopher P. Montgomery
Summary: Recurrent S. aureus infections are common and existing immune responses are insufficient; candidate vaccines have failed, indicating a need to understand the bacterium's interaction with the host immune system; T cells play a critical role in determining susceptibility to infection, outlining the steps necessary for a T cell-mediated immune response in this review.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Di Ren, Julia Fedorova, Kayla Davitt, Tran Ngoc Van Le, John H. Griffin, Patricia Chia-Ying Liaw, Charles Esmon, Alireza R. Rezaie, Ji Li
Summary: This study investigates the role of the APC-EPCR axis in ischemic insults in aging. The results show that APC activity is reduced during cardiac ischemia and reperfusion, and this reduction is more pronounced in aged hearts. Administration of APC prevents the shedding of EPCR induced by I/R and improves cardiac dysfunction in both young and aged mice. However, these cardioprotective effects of APC are diminished in EPCRR84A/R84A mice. AMPK mediates acute adaptive response while AKT is involved in chronic metabolic programming in APC-treated hearts.
CIRCULATION RESEARCH
(2022)
Article
Cell Biology
Junxiu Nong, Kexin Kang, Qiaoni Shi, Xuechen Zhu, Qinghua Tao, Ye-Guang Chen
Summary: The liquid-liquid phase separation of Axin drives the formation of the destruction complex, facilitating the recruitment of other members and promoting phosphorylation of beta-catenin, critical for regulating Wnt/beta-catenin signaling.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Taegwan Yun, Hyo Rim Ko, Dong-Kyu Jo, Kye Won Park, Sung-Woo Cho, Jihoe Kim, Jee-Yin Ahn
Summary: This study identified Id2 as a novel MT-binding partner that enhances alpha K40 acetylation, promoting MT polymerization in neurons. The research suggests that Id2 is critical for maintaining MT stability during neural development and has the potential to counteract pathogenic Sirt2 activity in Alzheimer's disease (AD).
CELL DEATH DISCOVERY
(2021)
Review
Plant Sciences
Jincheng Li, Manqi Zhang, Lijuan Zhou
Summary: Protein S-acylation, also known as palmitoylation, is a vital lipid post-translational modification in eukaryotes, playing critical roles in plant development and responses to various stresses. The dynamic and reversible nature of S-acylation allows membrane-associated proteins to undergo cycling and trafficking, acting as a switch in signaling transductions. While numerous S-acylated proteins have been identified in plants, the understanding of the regulatory mechanisms controlling this process remains incomplete.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Evolutionary Biology
Rafael Eiji Iwama, Michael Tessler, Mark E. Siddall, Sebastian Kvist
Summary: Blood-feeding parasites have evolved specific molecular features, such as anticoagulatory proteins, to inhibit host hemostasis in order to efficiently feed on blood. The antistasin-like protein family, found in bloodfeeding insects, bats, and leeches, is also present in non-bloodfeeding invertebrates like cnidarians and mollusks. The study aims to understand the evolution of antistasin-like proteins in leeches, identifying distinct clades and potential independent origins of salivary proteins secreted by leeches.
GENOME BIOLOGY AND EVOLUTION
(2021)
Article
Biochemistry & Molecular Biology
Johana Hrdinova, Delia I. Fernandez, Bogac Ercig, Bibian M. E. Tullemans, Dennis P. L. Suylen, Stijn M. Agten, Kerstin Jurk, Tilman M. Hackeng, Karen Vanhoorelbeke, Jan Voorberg, Chris P. M. Reutelingsperger, Kanin Wichapong, Johan W. M. Heemskerk, Gerry A. F. Nicolaes
Summary: This study designed and synthesized stable cyclic peptides to interfere with the interaction between VWF A1 domain and GPIb alpha. The selected peptides showed low binding free energy and retained their interference in the binding of VWF to GPIb-V-IX, as confirmed by flow cytometry. These peptides phenotypically mimicked the changes seen with the anti-VWF A1 domain antibody CLB-RAg35, although they were less potent. The improved peptide opt-mono-ORbIT demonstrated increased inhibitory activity under flow.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dawid M. Kaczor, Rafael Kramann, Tilman M. Hackeng, Leon J. Schurgers, Rory R. Koenen
Summary: Platelet factor 4 (CXCL4) is a chemokine stored in platelets that modulates the function of vascular smooth muscle cells (VSMCs). Variant CXCL4L1, despite minor differences, has distinct effects on VSMCs compared to CXCL4. Both CXCL4 and CXCL4L1 regulate gene expression, but only CXCL4 increases VSMC proliferation and calcification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Shahzad Hafeez, Huey Wen Ooi, Dennis Suylen, Hans Duimel, Tilman M. Hackeng, Clemens van Blitterswijk, Matthew B. Baker
Summary: Supramolecular materials based on BTA offer a way to mimic fibrous proteins found in nature, but current methods face limitations in BTA structure diversity and purification. We developed a desymmetrization method using activated ester coupling to rapidly synthesize multifunctional BTAs. These BTAs can self-assemble into hydrogels that display fiber-like structures and high cytocompatibility, making them suitable for tissue engineering applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Hematology
Anja Maag, Nienke van Rein, Tim J. Schuijt, Wil F. Kopatz, Danielle Kruijswijk, Stella Thomassen, Tilman M. Hackeng, Rodney M. Camire, Tom van der Poll, Joost C. M. Meijers, Mettine H. A. Bos, Cornelis van't Veer
Summary: Plasma thrombin generation provides important information on coagulation status, but current parameters do not predict major bleeding in patients on anticoagulants. Activation of factor V by factor Xa contributes significantly to thrombin generation, with greater activation associated with increased risk of major bleeding during VKA therapy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Sophie C. Dolleman, Stijn M. Agten, Henri M. H. Spronk, Tilman M. Hackeng, Mettine H. A. Bos, Henri H. Versteeg, Anton Jan van Zonneveld, Hetty C. de Boer
Summary: This study investigated the potential effects of different DOACs on vascular integrity. The results showed that the anti-FXa DOAC rivaroxaban preserved endothelial barrier function, while the anti-thrombin DOAC dabigatran failed to protect endothelial integrity over time. However, the loss of barrier function caused by dabigatran could be prevented by a mimicking peptide that blocks thrombin's exosite-I.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Julian Leberzammer, Stijn M. Agten, Xavier Blanchet, Rundan Duan, Hans Ippel, Remco T. A. Megens, Christian Schulz, Maria Aslani, Johan Duchene, Yvonne Doring, Natalie J. Jooss, Pengyu Zhang, Richard Brandl, Konstantin Stark, Wolfgang Siess, Kerstin Jurk, Johan W. M. Heemskerk, Tilman M. Hackeng, Kevin H. Mayo, Christian Weber, Philipp von Hundelshausen
Summary: The study explored the molecular mechanisms of CXCL12 in arterial thrombosis, revealing that inhibition of CXCR4 can attenuate platelet aggregation and limit arterial thrombosis. Mechanistically, CXCL12 activates Btk leading to platelet aggregation, while the interaction between CXCL12 and CCL5 can inhibit this process. A novel peptide was found to inhibit CXCL12-induced platelet aggregation without prolonging bleeding time.
Article
Hematology
Josepha C. Sedzro, Frederic Adam, Claire Auditeau, Elsa Bianchini, Allan De Carvalho, Ivan Peyron, Sadyo Darame, Sophie Gandrille, Stella Thomassen, Tilman M. Hackeng, Olivier D. Christophe, Peter J. Lenting, Cecile Denis, Delphine Borgel, Francois Saller
Summary: The research team generated a PS-specific sdAb (PS003) that enhances the APC-cofactor activity of PS, showing an anti-thrombotic effect in a mouse model. This innovative approach might represent a promising and safe antithrombotic strategy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Multidisciplinary Sciences
Judy R. van Beijnum, Elisabeth J. M. Huijbers, Karlijn van Loon, Athanasios Blanas, Parvin Akbari, Arno Roos, Tse J. Wong, Stepan S. Denisov, Tilman M. Hackeng, Connie R. Jimenez, Patrycja Nowak-Sliwinska, Arjan W. Griffioen
Summary: Anti-angiogenic cancer therapies have immune-stimulatory properties. This study found that tumor endothelial cells overexpress and secrete the protein vimentin, which promotes angiogenesis and inhibits leukocyte-endothelial interactions. Targeting extracellular vimentin shows inhibition of angiogenesis and tumor growth, and induces a pro-inflammatory condition in the tumor.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Robert Dzhanaev, Christian Hasberg, Andrea Gorgels, Carlo Schmitz, Camilla Franziska Winkler, Hanna Malyaran, Steffen Graeber, Anouk Gentier, Armand Jaminon, Stijn Agten, Tilman Hackeng, Asim Cengiz Akbulut, Leon Schurgers, Felix Manuel Mottaghy, Claudia Goettsch, Willi Jahnen-Dechent
Summary: This study developed a novel highly sensitive fluorescent probe based on fetuin-A for imaging microcalcifications. The probe showed non-toxicity and the ability to detect microcalcifications beyond the detection limit of conventional staining techniques. This fetuin-A-based probe has the potential for clinical applications.
Article
Engineering, Biomedical
Tianyu Yao, Honglin Chen, Rong Wang, Rebeca Rivero, Fengyu Wang, Lilian Kessels, Stijn M. Agten, Tilman M. Hackeng, Tim G. A. M. Wolfs, Daidi Fan, Matthew B. Baker, Lorenzo Moroni
Summary: This study focuses on the functionalization of scaffolds using a polymer mixing approach to immobilize VEGF-mimetic peptides. The functionalized scaffolds were validated and tested, showing potential for promoting angiogenesis and vascular tissue regeneration.
BIOACTIVE MATERIALS
(2023)
Article
Hematology
Tom W. Van de Berg, Erik A. M. Beckers, Floor C. J. I. Heubel-Moenen, Yvonne M. C. Henskens, M. Christella L. G. D. Thomassen, Tilman M. Hackeng
Summary: This study aims to optimize thrombin generation assays (TGAs) for better measurement of low factor VIII (FVIII) levels in severe hemophilia A (HA) patients. The use of low concentrations of tissue factor (TF) and FXIa appears to increase the sensitivity of TG to detect changes in low FVIII ranges.
THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Nutrition & Dietetics
Lu Dai, Denise Mafra, Paul G. Shiels, Tilman M. Hackeng, Peter Stenvinkel, Leon J. Schurgers
Summary: Vitamin K and vitamin K-dependent proteins are associated with age-related diseases. The direct impact of vitamin K on cellular senescence is yet to be proven, but its status reflects the complex interactions between dietary intake, gut microbiome activity, and health. It is proposed to emphasize food quality and explore healthy eating patterns containing vitamin K rather than focusing on a single nutrient for dietary recommendations.
Article
Chemistry, Medicinal
Jinwei Chai, Jiena Wu, Jinqiao Li, Hang Liao, Wancheng Lu, Ruiyin Guo, Zuoyan Shao, Mohamed Amine Jmel, Larissa Almeida Martins, Tilman Hackeng, Hans Ippel, Ingrid Dijkgraaf, Michail Kotsyfakis, Xueqing Xu
Summary: A novel Ranacyclin peptide called Ranacin was identified from the skin of Pelophylax nigromaculatus frog. Ranacin effectively inhibited trypsin and exhibited anticoagulant and antioxidant activities in vitro. Treatment with Ranacin significantly alleviated the severity of pancreatitis in L-Arg-induced AP mice. Structure-activity studies suggested that sequences outside the trypsin inhibitory loop (TIL) of Ranacin may play an important role in its efficacy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Hematology
M. Christella L. G. D. Thomassen, Bryan R. C. Bouwens, Kanin Wichapong, Dennis P. Suylen, Freek G. Bouwman, Tilman M. Hackeng, Rory R. Koenen
Summary: This study found that PAD4 inactivates TFPI by citrullination of its arginines, and this process is time- and concentration-dependent. Furthermore, inducers of PAD4 blocked the citrullination of TFPI. This process may play a crucial role in the increased thrombosis risk associated with inflammation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Nutrition & Dietetics
Julie Ann Kemp, Livia Alvarenga, Ludmila F. M. F. Cardozo, Lu Dai, Peter Stenvinkel, Paul G. Shiels, Tilman M. Hackeng, Leon J. Schurgers, Denise Mafra
Summary: This narrative review summarizes the current evidence on the connection between dysbiosis and vitamin K deficiency in patients with chronic kidney disease (CKD). Recent studies in animals have shown that dysbiosis is associated with low production of vitamin K by the gut microbiota. Vitamin K plays vital roles in blood coagulation, cardiovascular and bone health, as well as antioxidant and anti-inflammatory functions. The main source of vitamin K is dietary intake, but it can also be produced by gut microbiota. Understanding the relationship between gut dysbiosis and vitamin K deficiency in CKD patients can lead to future clinical studies.
CURRENT NUTRITION REPORTS
(2022)
Article
Hematology
E. O. Artemenko, S. I. Obydennyi, K. S. Troyanova, G. A. Novichkova, D. Y. Nechipurenko, M. A. Panteleev
Summary: In this study, we investigated the adhesive properties of circulating plasma-derived and platelet-derived microvesicles (MVs) and their potential role in thrombus growth. The results showed that both types of MVs weakly bound fibrinogen but did not stably adhere to immobilized fibrinogen. Moreover, the presence of these MVs did not significantly affect thrombus formation. Therefore, MVs present in the plasma of healthy individuals are unlikely to directly contribute to thrombus formation under arterial flow conditions.
THROMBOSIS RESEARCH
(2024)
Letter
Hematology
Giuseppe Lippi, Camilla Mattiuzzi, Emmanuel J. Favaloro
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Marium Malik, Maha Al-Ghafry, Abraham Haimed, Julia Su, Maribel Lema, Linda Shore-Lessersson, Suchitra S. Acharya
Summary: This study analyzed and evaluated leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCTs and ROTEM. The results showed that fibrinogen and platelets played a significant role in causing coagulopathies in this population. This suggests the utility of using CCTs and ROTEM in the pediatric population to evaluate hemostatic function and guide blood product replacement.
THROMBOSIS RESEARCH
(2024)
Review
Hematology
Mohammad M. Elahi, Alexandra N. Witt, Edward L. G. Pryzdial, Paul B. McBeth
Summary: Thrombotic disease may be underdiagnosed in microgravity conditions, and the underlying factors are still poorly understood. A case of internal jugular vein thrombosis was recently diagnosed in a low-risk female astronaut, and six out of ten additional crew members showed risk factors for jugular venous flow. Observations in space and studies on Earth suggest that microgravity affects blood flow, coagulation, and vascular function.
THROMBOSIS RESEARCH
(2024)
Review
Hematology
Stian Ingemann-Molden, Christina Krogner Caspersen, Nanna Rolving, Anette Arbjerg Hojen, Frederikus A. Klok, Erik L. Grove, Barbara Cristina Brocki, Jane Andreasen
Summary: This study found that no single PROM covered all aspects considered important by PE patients. PROMs recommended in the ICHOM core set covered most aspects, but worrisome thoughts, hypervigilance around symptoms, and uncertainty of illness were not covered.
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Haomin Yan, Tsutomu Sasaki, Yasufumi Gon, Kumiko Nishiyama, Hideaki Kanki, Hideki Mochizuki
Summary: The incidence of cancer-associated stroke has increased with the prolonged survival times of cancer patients. In this study, the researchers focused on the driver gene KRAS and found that KRAS mutations exacerbated neurological deficits after stroke and promoted tumor growth. They also identified the upregulation of pro-inflammatory responses and the promotion of STAT3 phosphorylation in mice with KRAS mutations. Additionally, the researchers found that colorectal cancer patients with stroke onset within 3 months after cancer diagnosis had a worse prognosis.
THROMBOSIS RESEARCH
(2024)
Letter
Hematology
Tomoki Togashi, Satomi Nagaya, Makiko Meguro-Horike, Haruto Matsumoto, Yuta Imai, Koichi Yamaguchi, Yoshinari Fujii, Haruka Moriya, Yuika Kikuchi, Ibuki Yasuda, Shin-ichi Horike, Eriko Morishita
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Marta Najarro, Winnifer Briceno, Carmen Rodriguez, Alfonso Muriel, Sara Gonzalez, Ana Castillo, Ignacio Jara, Parth Rali, Catalin Toma, Behnood Bikdeli, David Jimenez
Summary: The CPES score is a useful tool in identifying the risk of hemodynamic deterioration in normotensive patients with acute PE, with acceptable C-statistic, excellent specificity, and low positive predictive value.
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Lei Liu, Huifang Xu, Jian Wang, Haiyan Wang, Saisai Ren, Qian Huang, Mingyan Zhang, Hui Zhou, Chunyan Yang, Lu Jia, Yu Huang, Hao Zhang, Yanling Tao, Ying Li, Yanan Min
Summary: This study investigated the gut microbiota metabolites and cytokines, chemokines, and growth factors in patients with ITP and found their association with treatment responsiveness. The findings suggest that imbalanced secretion of cyto(chemo)kins/growth factors and inadequate levels of TMAO are characteristic of patients with ITP.
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Roxanne Mcknight, Mohammad Salameh, Lee Ann Jones, Greta Anton, Lindsay Carter
Summary: This study evaluated the safety of fixed-dose heparin titration boluses in underweight patients with VTE. The results showed that although underweight patients required more frequent holding of heparin, there was no significant increase in bleeding risk.
THROMBOSIS RESEARCH
(2024)
