Article
Hematology
Ruiqi Yin, Vishal Patel, Rida A. Malik, James C. Fredenburgh, Jeffrey I. Weitz
Summary: Polyphosphate (polyP) serves as a template to promote feedback activation of factor XI by thrombin. This study determines the contribution of thrombin exosites 1 and 2 to polyP-induced potentiation of FXI activation. The results show that polyP accelerates FXI activation by thrombin and exosite 2 ligands attenuate this activation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Materials Science, Biomaterials
Mengchi Lin, Lisha Yu, Liping Xiao, Jie Fan
Summary: We report an easy-to-use and heparin-tolerant hemostatic agent based on a thrombin-like cysteine enzyme (papain), which effectively stops bleeding by catalyzing the hydrolysis of fibrinogen and cross-linking of fibrin clots. The hemostatic agent, immobilized on a cellulose carrier, displays short clotting time in both normal and heparinized plasmas. It shows excellent hemostatic performance in various animal models where the natural coagulation system fails to function due to heparin, indicating its great potential as a bio-hemostat to rapidly stop bleeding in surgical procedures.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Chemistry, Medicinal
Elsamani I. Abdelfadiel, Rama Gunta, Bharath Kumar Villuri, Daniel K. Afosah, Nehru Viji Sankaranarayanan, Umesh R. Desai
Summary: Natural glycosaminoglycans (GAGs) are a diverse group of natural products that have not been fully utilized. Research has only led to the development of one GAG-like synthetic drug, highlighting the difficulty in working with GAGs. This Perspective aims to transform the negative perception of GAGs by highlighting recent advances in GAG mimetics, specifically in the design of synthetic sulfated small molecules as allosteric modulators of coagulation factors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Critical Care Medicine
Troy G. Seelhammer, John K. Bohman, Phillip J. Schulte, Andrew C. Hanson, Devon O. Aganga
Summary: The study compared the effects of conventional heparin and bivalirudin anticoagulants in adult and pediatric patients receiving extracorporeal membrane oxygenation support. The adult group using bivalirudin showed reduced hospital mortality, while the pediatric group had decreased transfusion requirements in the first 24 hours. No significant differences were found between the two groups in terms of age, sex, and treatment-related complications.
CRITICAL CARE MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Theodore Tyrikos-Ergas, Eric T. Sletten, Jhih-Yi Huang, Peter H. Seeberger, Martina Delbianco
Summary: Sulfated glycans play important roles in many biological processes, and well-defined sulfated oligosaccharides are highly sought molecular probes. This study presents a general on-resin approach to simplify the synthesis of sulfated glycans, resulting in the successful synthesis of seven diverse sulfated glycans.
Article
Biophysics
Anran Zheng, Wei Zhang, Chao Li, Zhen Guo, Chuanyu Li, Changsong Zhang, Jia Yao, Zhiqi Zhang, Jinze Li, Shasha Zhao, Lianqun Zhou
Summary: A novel HLDT method was developed using a GR-C sensor to quantitatively evaluate heparin potency in whole blood. The method demonstrated high selectivity for heparin potency in 10 μL of whole blood with a detection limit of 0.1 U/mL.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Cardiac & Cardiovascular Systems
Christine S. Ji, Russel J. Roberts, Megan E. Barra, Hang Lee, Rachel P. Rosovsky
Summary: This study evaluated the safety and efficacy of direct thrombin inhibitors (DTIs) during a heparin shortage, finding that while there was an increase in the use of DTIs within the initial 48 hours of therapy, there were no significant differences in patient safety and effectiveness.
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2021)
Review
Biochemistry & Molecular Biology
Hannah L. McRae, Leah Militello, Majed A. Refaai
Summary: Heparin and warfarin were traditionally used as primary anticoagulants, but the emergence of newer oral and parenteral anticoagulants has led to shifts in practice guidelines and monitoring needs, creating challenges in knowledge and resources for urgent reversal and monitoring in clinical scenarios.
Article
Biochemistry & Molecular Biology
Romualdo Troisi, Nicole Balasco, Luigi Vitagliano, Filomena Sica
Summary: This study utilized molecular dynamics simulations to investigate the dynamic interactions of thrombin with aptamers TBA and HD22_27mer in binary/ternary complexes, revealing the mechanism of stabilization of these complexes in a crystal-free environment. The dynamics analysis indicated a communication between the exosites in different thrombin binding states, providing insights into the cooperativity of TBA/HD22_27mer binding experimentally detected.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Review
Biochemistry & Molecular Biology
Romualdo Troisi, Nicole Balasco, Ida Autiero, Luigi Vitagliano, Filomena Sica
Summary: This study investigates the structural determinants of thrombin partnerships with various ligands, focusing on the interaction between thrombin and exosite ligands, especially the specificity of thrombin binding to aptamers. The research reveals new insights into the design of thrombin inhibitors and the interface area between thrombin and exosite ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yongqi Zhang, Jia Man, Jiali Wang, Jianing Liu, Xinzhong Song, Xiaohan Yu, Jianyong Li, Ruijian Li, Yinghua Qiu, Jianfeng Li, Yuguo Chen
Summary: This study developed heparinized surfaces on PVC substrates using plasma treatment technology and chemical grafting method. The heparinized surfaces not only reduced thrombosis but also decreased side effects of anticoagulants. Sodium alginate and carboxymethyl chitosan interlayers significantly increased the graft density of heparin, improving its anticoagulant effects and hemocompatibility. The CCS/low-molecular-weight heparin surface showed the best anticoagulant properties. The heparinized surfaces prepared in this study have great potential in anticoagulant treatment for medical devices.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Agricultural Engineering
Yuyang Fan, Ming Lei, Yue Han, Zhengxue Zhang, Xiangchen Kong, Weicong Xu, Ming Li, Huiyan Zhang, Rui Xiao, Chao Liu
Summary: The effect of lignin preoxidation on subsequent radical-mediated pyrolysis was investigated in this study. The findings showed that preoxidation modified the structure of lignin, reduced its thermal stability and pyrolysis reactivity, and shifted lignin decomposition towards lower temperatures, inhibiting the formation of bio-oil fractions. However, the reaction pathways remained unchanged. The study also analyzed the gas compositions and monitored the radicals in chars and bio-oils, finding that char radical concentrations were proportional to the degree of preoxidation.
BIORESOURCE TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiawei Xu, Wei Ye, Ting Ting Yang, Teng Yan, Haiyan Cai, Aiwu Zhou, Yufeng Yang
Summary: In this study, a bacterial serpin called chloropin was identified and its crystal structure was determined. Chloropin showed inhibitory activity against multiple proteases and could be accelerated by DNA. These findings suggest that DNA may be a natural modulator of chloropin and prokaryotic serpins have evolved to use different surface subsites for activity modulation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Yongqi Zhang, Jia Man, Jianing Liu, Jianyong Li, Xinzhong Song, Jiali Wang, Jianfeng Li, Yuguo Chen
Summary: In this study, a mussel-inspired composite coating consisting of polydopamine, lysine, and modified heparin was constructed to reduce thrombosis and enhance the anticoagulant capability of medical devices. The results showed that the composite coating significantly inhibited platelet adhesion and activation, prolonged activated partial thromboplastin time, and exhibited excellent hemocompatibility and anticoagulant properties. This research demonstrates great potential for anticoagulant treatment in medical devices.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Zeyuan Mo, Zhenbang Xiao, Chunmao He
Summary: Triabin, a lipocalin-like thrombin inhibitor found in the saliva of Triatoma pallidipennis, shows potent inhibition comparable to hirudin by binding exclusively at exosite I. It has the potential to be an effective antithrombotic agent with a larger therapeutic window. However, limited structural and functional studies on triabin have been conducted due to the lack of a reliable recombinant expression technology. In this study, the researchers successfully expressed and purified bioactive triabin using the SUMO fusion technology, revealing the crucial role of Phe-106 in thrombin inhibition. This study enhances our understanding of natural thrombin inhibitors and may contribute to the development of novel anticoagulant drugs.
Article
Biochemistry & Molecular Biology
Balaji Nagarajan, Nehru Viji Sankaranarayanan, Umesh R. Desai
Summary: GAGs exhibit a high level of conformational and configurational diversity, but it remains underexplored in terms of protein recognition and modulation. Only a few therapeutics have been designed or discovered so far. Recent studies on chondroitin sulfate (CS) have led to the investigation of the conformational dynamism of CS building blocks using molecular dynamics (MD). The results suggest that CS building blocks offer unique conformational dynamism that may provide unique electrostatic surfaces for protein recognition.
Article
Biochemistry & Molecular Biology
Balaji Nagarajan, Samuel G. Holmes, Nehru Viji Sankaranarayanan, Umesh R. Desai
Summary: This article discusses the use of molecular dynamics (MD) to understand the properties of glycosaminoglycans (GAGs) in free solution and their interaction with proteins. The results of MD studies suggest that the recognition of GAGs by proteins varies from highly selective to fully non-selective, with intermediate levels of selectivity and plasticity.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Rio S. Boothello, Nehru Viji Sankaranarayanan, Jyothi C. Sistla, Balaji Nagarajan, Chetna Sharon, John E. Chittum, Rabiya Y. Niyaz, Swarnali Roy, Aditi Nandi, Connor P. O'Hara, Rahaman Navaz Gangji, Daniel K. Afosah, Ravikumar Ongolu, Bhaumik B. Patel, Umesh R. Desai
Summary: This study reveals the inhibitory effect of shorter soluble heparan sulfate sequences on IGF-1R, contrary to the traditional relationship. Smaller oligosaccharides competitively bind in a unique pocket in the IGF-1R structure, inhibiting its activation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Shravan Morla, Ongolu Ravikumar, Connor O'Hara, Rio Boothello, Alberto Vera, Elsamani I. Abdelfadiel, Rawan Fayyad, Daniel K. Afosah, Chetna Sharon, Leopoldo Fernandez, Syed Ammer Shah, Bhaumik B. Patel, Umesh R. Desai
Summary: Conjugating cholesterol to synthetic sulfated glycosaminoglycan (GAG) mimetics enables oral delivery and shows excellent anticancer potential both in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Elsamani I. Abdelfadiel, Rama Gunta, Bharath Kumar Villuri, Daniel K. Afosah, Nehru Viji Sankaranarayanan, Umesh R. Desai
Summary: Natural glycosaminoglycans (GAGs) are a diverse group of natural products that have not been fully utilized. Research has only led to the development of one GAG-like synthetic drug, highlighting the difficulty in working with GAGs. This Perspective aims to transform the negative perception of GAGs by highlighting recent advances in GAG mimetics, specifically in the design of synthetic sulfated small molecules as allosteric modulators of coagulation factors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Nagendraprabhu W. Ponnuraj, Haji Akbar, Justine F. Arrington, Stephen Spatz, Balaji F. Nagarajan, Umesh Desai, Keith F. Jarosinski
Summary: The study reveals that the conserved Herpesviridae protein kinase (CHPK) is a crucial factor for Marek's disease herpesvirus (MDV) in chicken infection, and the removal of the US10 protein from MDV reduces its virulence. Understanding these viral proteins and their functions during infection is important for elucidating the infection mechanism and developing therapeutic strategies.
Article
Biochemistry & Molecular Biology
Daniel K. Afosah, Rawan M. Fayyad, Valerie R. Puliafico, Spencer Merrell, Eltice K. Langmia, Sophie R. Diagne, Rami A. Al-Horani, Umesh R. Desai
Summary: Researchers identified a synthetic molecule, octasulfated di-quercetin NSGM 25, which effectively inhibits CatG as well as other pro-inflammatory proteases. NSGM 25 demonstrated no bleeding risk and could potentially be used for a multi-pronged anti-inflammatory approach in treating various inflammatory disorders.
Article
Biochemistry & Molecular Biology
Nehru Viji Sankaranarayanan, Srinivas Sistla, Balaji Nagarajan, John E. Chittum, Joseph T. Y. Lau, Umesh R. Desai
Summary: Using our in-house combinatorial virtual library screening (CVLS) technology, we discovered that glycosaminoglycans (GAGs) may interact with sialyl transferases (STs) to varying degrees. Our detailed CVLS and molecular dynamics studies found that the common hexasaccharide sequence of heparan sulfate (HS) preferentially binds to ST6GAL1. This novel finding is important for understanding the physiological/pathological consequences of modulating sialylation of glycan substrates on cells.
Meeting Abstract
Oncology
Connor O'Hara, Shravan Morla, Ravikumar Ongolu, Nirmita Patel, Rio Boothello, Bhaumik Patel, Umesh Desai
Meeting Abstract
Biochemistry & Molecular Biology
Daniel K. Afosah, Valerie Puliafico, Spencer Merrell, Eltice Langmia, Rawan Fayyad, Rami A. Al-horani, Umesh R. Desai
Meeting Abstract
Biochemistry & Molecular Biology
Pavani Pingali, Jackson Faulx, Aditi Nandi, Shoja Haneefa, Won Lee, Adam Khader, Ammer Shah, Umesh R. Desai, Bhaumik B. Patel
Meeting Abstract
Biochemistry & Molecular Biology
Michael E. Rusiniak, Nehru Viji Sankaranarayanan, Srinivas Sistla, Amy Freeland, John E. Chittum, Ding Xu, Karin Hoffmeister, Umesh R. Desai, Joseph T. Y. Lau
Article
Biochemistry & Molecular Biology
Samuel G. Holmes, Balaji Nagarajan, Umesh R. Desai
Summary: This study discovered novel compact topologies of heparan sulfate (HS) that are influenced by the 3-O-sulfation of cis-idoA residues. The transition in HS topology is driven by rotations that reduce like-charge repulsion, release water molecules, and establish specific interactions. These findings reveal a dynamic sulfation code in natural HS that could be utilized for selective recognition of target proteins.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Samuel Holmes, Balaji Nagarajan, Umesh R. Desai
Meeting Abstract
Oncology
Connor P. O'Hara, Nehru V. Sankaranarayanan, Rio S. Boothello, Bhaumik B. Patel, Umesh R. Desai
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)