Article
Hematology
Bjorn Dahlback, Sinh Tran
Summary: The research elucidated the mechanisms behind the synergistic activity between FV756-1458 and protein S as TFPI alpha cofactors, showing that the presence of the preAR2 region is crucial for this synergism.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Bjorn Dahlback, Sinh Tran
Summary: This study aimed to identify the specific part of preAR2 required for the synergistic TFPI alpha-cofactor activity between FV-short and protein S. Results showed that FV709-1476, FV712-1478, and FV712-1481 exhibited full synergistic activity with protein S, while FV712-1484 showed intermediate activity and FV712-1487 and FV712-1490 were inactive.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Chemistry, Multidisciplinary
S. Mallik, R. Prasad, K. Das, P. Sen
Summary: The hydroxyl functionality of cell-surface sphingomyelin plays a role in forming a tight assembly through intermolecular hydrogen bonding and calcium chelation, which limits protein-lipid/protein-protein interactions and thus inhibits the coagulation process.
Article
Multidisciplinary Sciences
Xue Yan Cui, Geir Erland Tjonnfjord, Sandip M. Kanse, Anders Erik Astrup Dahm, Nina Iversen, Christiane Filion Myklebust, Ling Sun, Zhong Xing Jiang, Thor Ueland, James J. Campbell, Mitchell Ho, Per Morten Sandset
Summary: Plasma TFPI levels are higher in CLL patients compared to healthy controls, especially in those with advanced disease. TFPI enhances CXCL12-mediated migration of CLL cells through increased expression of the CXCR7 receptor. TFPI, which co-localizes with GPC3, plays a crucial role in regulating CXCR7 expression and TEM.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Hiroshi Kobayashi, Sho Matsubara, Chiharu Yoshimoto, Hiroshi Shigetomi, Shogo Imanaka
Summary: This review summarizes the biological functions of TFPI1 and TFPI2 in preeclamptic patients and discusses future directions in preeclampsia research. TFPI1 is an important physiological inhibitor of the TF-initiated extrinsic coagulation pathway, while TFPI2 inhibits fibrinolysis and exerts antifibrinolytic activity. TFPI1 and TFPI2 may play important roles in regulating the coagulation and fibrinolytic system and trophoblast invasion. Concentrations of TF, TFPI1, and TFPI2 are significantly altered in preeclamptic women compared to normal pregnancies. The TFPI protein family may serve as predictive biomarkers for preeclampsia and guide precision therapy.
Article
Immunology
Abhinandan Chowdhury, Matthew R. Lewin, Christina N. Zdenek, Rebecca Carter, Bryan G. Fry
Summary: African spitting cobras have potent anticoagulant venom activity due to strong inhibition of Factor Xa by venom phospholipase A(2) toxins, which current antivenoms cannot neutralize. Research has expanded this trait to include more cobras and found that enzyme-inhibitors can effectively counteract the toxic effects. This suggests potential alternative treatments for snakebite envenoming beyond traditional antivenoms.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Marie-Claire Dagher, Atanur Ersayin, Landry Seyve, Mathieu Castellan, Cyril Moreau, Luc Choisnard, Nicole Thielens, Raphael Marlu, Benoit Polack, Aline Thomas
Summary: By using computational chemistry and experimental approaches, a GD-FXa variant with improved anti-TFPI affinity was successfully designed and tested. The variant showed enhanced thrombin generation by prolonging its half-life through increased interaction with TFPI.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Oncology
Tao Wang, Peng Zhang, Chengguo Li, Weizhen Liu, Qian Shen, Lei Yang, Gengchen Xie, Jie Bai, Ruidong Li, Kaixiong Tao, Yuping Yin
Summary: MUS81 is a key regulator of cell cycle distribution and DNA damage repair in gastric cancer. Inhibition of MUS81 enhances the anticancer effect of the PARP inhibitor talazoparib by impairing the activation of the ATR/CHK1 cell cycle signaling pathway and promoting continued mitosis in gastric cancer cells with talazoparib-induced DNA damage. Additionally, the combination of the bromodomain-containing protein 4 inhibitor AZD5153 with talazoparib further enhances the anticancer effect, which is largely impaired when MUS81 is knocked down.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Yahya Madkhali, Araci M. R. Rondon, Sophie Featherby, Anthony Maraveyas, John Greenman, Camille Ettelaie
Summary: Under normal conditions, blood coagulation is suppressed to prevent thrombosis, but TF is released into the bloodstream during inflammatory conditions to modulate cellular fate. Cells regulate the procoagulant and signalling activity of TF by controlling its release levels.
Article
Hematology
Rui Terada, Penny M. Johnson, Amir L. Butt, Yuko Mishima, Kenneth E. Stewart, Jerold H. Levy, Kenichi A. Tanaka
Summary: This study demonstrates the feasibility of assessing coagulation lag time recovery in plasma and whole blood following in vitro apixaban reversal using GDXa, a biosimilar to andexanet. However, GDXa-induced changes in plasmin generation and fibrinolysis were limited, supporting the endogenous profibrinolytic activity of FXa and its inhibition at elevated apixaban concentrations.
THROMBOSIS RESEARCH
(2023)
Article
Endocrinology & Metabolism
You Jee Jang, Hee Kyung Kim, Bum Chae Choi, Sang Jin Song, Jae Il Park, Sang Young Chun, Moon Kyoung Cho
Summary: The study found that tissue factor and Tfpi-2 expression are stimulated during ovulation in rats, while tissue factor levels are decreased in OHSS-induced rats. Interestingly, tissue factor concentrations in follicular fluids of women undergoing in vitro fertilization are correlated with pregnancy but not with OHSS.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wineke Bakker, Calinda K. E. Dingenouts, Kirsten Lodder, Karien C. Wiesmeijer, Alwin de Jong, Kondababu Kurakula, Hans-Jurgen J. Mager, Anke M. Smits, Margreet R. de Vries, Paul H. A. Quax, Marie Jose T. H. Goumans
Summary: In HHT1, deficiency of endoglin leads to immune cell imbalance, particularly an excessive increase in inflammatory macrophages, which hinders tissue repair. Inhibiting BMP signaling restores macrophage balance and improves tissue repair after ischemic injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Tiffany Toni, Ramya Viswanathan, Yvette Robbins, Sreenivasulu Gunti, Xinping Yang, Angel Huynh, Hui Cheng, Anastasia L. Sowers, James B. Mitchell, Clint T. Allen, Ethan L. Morgan, Carter Van Waes
Summary: In this study, dual treatment with IAP and WEE1 inhibitors was found to enhance the sensitivity of head and neck squamous cell carcinoma cells to TNF alpha-induced cell death, providing a potential therapeutic combination for the treatment of these cancers.
Article
Immunology
Lukas Muri, Emma Ispasanie, Anna Schubart, Christine Thorburn, Natasa Zamurovic, Thomas Holbro, Michael Kammueller, Gerd Pluschke
Summary: Two different physiological opsonophagocytosis assay formats yielded consistent results, emphasizing the importance of alternative complement pathway activation for efficient killing in vaccine-naive individuals. In contrast, alternative pathway inhibition did not affect pneumococcal killing in PCV13-vaccinated subjects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biophysics
Kenji Miyazawa, Aaron L. Fogelson, Karin Leiderman
Summary: Blood coagulation is a self-repair process regulated by activated platelet surfaces, clotting factors, and inhibitors. Recently, a new role for TFPI in inhibiting thrombin generation on activated platelet surfaces has been discovered, which is independent of TF:VIIa. This study found that this TF-independent inhibitory mechanism is more effective than the TF-dependent one.
BIOPHYSICAL JOURNAL
(2023)
