Article
Biochemistry & Molecular Biology
Marco Maccarana, Juan Jia, Honglian Li, Xiao Zhang, Israel Vlodavsky, Jin-Ping Li
Summary: Heparin, a polysaccharide expressed in animal connective tissue, specifically binds to antithrombin and enhances its inhibitory activity. This study examined the heparin isolated from different mast cells and found differences in molecular size and antithrombin-binding activity. Heparanase expression affected the production of glycosaminoglycans and the proportion between heparin and other glycosaminoglycans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Reka Gindele, Krisztina Penzes-Daku, Gabor Balogh, Judit Kallai, Reka Bogati, Balint Becsi, Ferenc Erdodi, Eva Katona, Zsuzsanna Bereczky
Summary: The study compared the molecular background of AT Budapest 3, AT Basel, and AT Padua mutations, finding that AT Padua had the lowest heparin affinity and most severe consequences on activation pathways, while AT Basel had slower heparin-binding but minor effects. Additionally, ATBp3 exhibited molecular instability with altered allosteric activation and decreased thermostability.
Article
Biochemistry & Molecular Biology
Jia Shi, Riku Kanoya, Yurina Tani, Sodai Ishikawa, Rino Maeda, Sana Suzuki, Fumiya Kawanami, Naoko Miyagawa, Katsuhiko Takahashi, Teruaki Oku, Ami Yamamoto, Kaori Fukuzawa, Motowo Nakajima, Tatsuro Irimura, Nobuaki Higashi
Summary: This study found that sulfated hyaluronan can inhibit the enzymatic and biological actions of heparanase, a key enzyme involved in cancer malignancy and inflammation. Sulfated hyaluronan effectively inhibits the degradation of heparan sulfate by human and mouse heparanase, and it can bind to heparanase molecules. In the presence of sulfated hyaluronan, the invasion of heparanase-positive cells and the release of CCL2 are significantly suppressed. The inhibitory effect is likely due to competitive binding between sulfated hyaluronan and heparanase molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sheng Yang, Yubo Tang, Yijun Liu, Abbigale J. Brown, Matthias Schaks, Bojian Ding, Daniel A. Kramer, Magdalena Mietkowska, Li Ding, Olga Alekhina, Daniel D. Billadeau, Saikat Chowdhury, Junmei Wang, Klemens Rottner, Baoyu Chen
Summary: This study reveals a new mechanism for WRC sensing Arf signaling and provides a mechanistic foundation for understanding how WRC-mediated actin polymerization links Arf and Rac signaling in cells.
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
Biochemistry & Molecular Biology
Jesper Bergwik, Amanda Kristiansson, Jorgen Larsson, Simon Ekstrom, Bo Akerstrom, Maria Allhorn
Summary: A1M can bind to heparin and HS, and can be purified from human plasma using heparin affinity chromatography and size exclusion chromatography. The binding strength is inversely proportional to salt concentration and directly proportional to the sulfation degree of heparin and HS.
Article
Medicine, General & Internal
Ivana Malikova, Martina Husakova, Jana Bilkova, Radka Brzezkova, Tomas Kvasnicka
Summary: This study aimed to determine the effectiveness of heparin by monitoring changes in thrombin generation in vitro, so that pregnant women are not exposed to stress in vivo. The results showed significant differences in the degree of inhibition among different heparins, with nadroparin being the most effective. Therefore, monitoring thrombin generation should be supplemented with routine anti-Xa activity monitoring to estimate thrombophilic risk during pregnancy.
MEDICAL PRINCIPLES AND PRACTICE
(2023)
Article
Medicine, Research & Experimental
Hongzhong Zhou, Yiqun Du, Xiafei Wei, Chunli Song, Jianning Song, Nanson Xu, Weihong Huang, Lichan Chen, Fuwen Yao, Duanming Du, Chuanghua Qiu, Lihong Zhong, Yuchen Liu, Dayong Gu, Jin Wang, Yong Xu
Summary: This study found that DDX56 is upregulated in hepatocellular carcinoma (HCC) tissues and is strongly correlated with poor prognoses for HCC patients. DDX56 promotes HCC cell proliferation by interacting with MECOM to mono-methylate H3K9 on the MIST1 promoter. Furthermore, ZEB1 binds to DDX56 and transcriptionally activates DDX56, leading to HCC tumorigenesis.
Article
Multidisciplinary Sciences
Tao Xu, Haifeng Ji, Lin Xu, Shengjun Cheng, Xianda Liu, Yupei Li, Rui Zhong, Weifeng Zhao, Jayachandran N. Kizhakkedathu, Changsheng Zhao
Summary: The authors have developed a carboxylated and sulfonated heparin-mimetic polymer-modified sponge for intraoperative auto-transfusion. This sponge exhibits spontaneous blood adsorption and instantaneous anticoagulation, effectively inhibiting the common coagulation pathway. It enables faster recovery of hemostasis compared to traditional heparinized blood, providing a safe and convenient approach for whole blood auto-transfusion.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Alexia Abecassis, Esther Hermano, Adi Yifrach, Aron Popovtzer, Amichay Meirovitz, Michael Elkin
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and treatment-resistant tumor with a very low survival rate. The unique pathophysiological features of PDAC, such as dense extracellular matrix and diabetic conditions, contribute to its poor prognosis. This study discovered that elevated levels of heparanase, an enzyme that degrades glycosaminoglycan in the extracellular matrix, in combination with diabetic conditions, promote the growth and chemotherapy resistance of pancreatic carcinoma by enhancing insulin receptor signaling and glucose uptake into tumor cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Doreen Tabea Spiegelburg, Marco Mannes, Anke Schultze, Frieder Scheibenberger, Frederik Mueller, Amadeo Klitzing, David Alexander Christian Messerer, Kristina Nilsson Ekdahl, Bo Nilsson, Markus Huber-Lang, Christian Karl Braun
Summary: This study evaluated the advantages and disadvantages of antithrombotic and antifouling surface coatings for ex vivo incubation and the study of coagulation properties. The MPC-based coatings demonstrated better hemocompatibility compared to the CHC-based coatings, and ENOX and FPX proved useful for additional anticoagulation. This simple-to-use whole blood model may be useful for experimental analyses of the early coagulatory and immunological response.
Article
Microbiology
Yuanyuan Lei, Li Tang, Shuang Liu, Shiping Hu, Lingyi Wu, Yaojiang Liu, Min Yang, Shengjie Huang, Xuefeng Tang, Tao Tang, Xiaoyan Zhao, Israel Vlodavsky, Shuo Zeng, Bo Tang, Shiming Yang
Summary: Heparanase exacerbates acute pancreatitis through its interaction with the gut microbiota, particularly the commensal Parabacteroides. In addition, Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis by reducing neutrophil infiltration, suggesting a potential therapeutic strategy for acute pancreatitis.
Article
Immunology
Jane Fisher, Fredrik Kahn, Elena Wiebe, Pontus Gustafsson, Thomas Kander, Lisa Mellhammar, Peter Bentzer, Adam Linder
Summary: The study revealed that in addition to neutrophils, monocytes can also release HBP, with the liver being responsible for the majority of its clearance. Further exploration is needed to understand the impact of hematologic malignancies and liver diseases on plasma HBP levels.
JOURNAL OF INNATE IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Md. Saddam Husain Ansari, Naveen Kumar, Sriyans Jain, N. Yogesh Balakarthick, Ranjan Sen
Summary: We screened a clone from a genomic library of mycobacteriophages and found it to have mycobactericidal properties. This clone codes for a protein called Gp49, which is highly conserved among mycobacteriophages and likely plays a role in phage DNA replication. Gp49 is a high-affinity heparin-binding protein that can bind to both linear dsDNA and ssDNA/cooperatively, inhibiting transcription and displacing DNA-binding proteins. Its heparin-binding ability could have therapeutic/diagnostic applications in bacterial sepsis treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Hematology
Lacramioara Ivanciu, Valder R. Arruda, Rodney M. Camire
Summary: In this study, we generated FIXa variants with altered reactivity to plasma inhibitors and found that delayed FIXa inhibition has a major impact on reducing bleeding and promoting thrombus formation.
Article
Oncology
David Zaragoza-Huesca, Andres Nieto-Olivares, Francisco Garcia-Molina, Guillermo Ricote, Sofia Montenegro, Manuel Sanchez-Canovas, Pedro Garrido-Rodriguez, Julia Penas-Martinez, Vicente Vicente, Francisco Martinez, Maria Luisa Lozano, Alberto Carmona-Bayonas, Irene Martinez-Martinez
Summary: This study investigated the role of hepsin in colorectal cancer and found that it is an independent prognostic factor for metastasis and thrombosis in patients with localized disease. Low levels of hepsin were associated with higher tumor dedifferentiation and spread to distant organs in metastatic patients. These findings suggest that hepsin could be a potential biomarker for complications in colorectal cancer patients.
Article
Cardiac & Cardiovascular Systems
Maria Eugenia de la Morena-barrio, Javier Corral, Cecilia Lopez-Garcia, Victor Alonso Jimenez-Diaz, Antonia Minano, Pablo Juan-Salvadores, Maria Asuncion Esteve-Pastor, Jose Antonio Baz-Alonso, Ana Maria Rubio, Francisco Sarabia-Tirado, Miguel Garcia-Navarro, Juan Garcia-Lara, Francisco Marin, Vicente Vicente, Eduardo Pinar, Sergio Jose Canovas, Gonzalo de la Morena
Summary: In this study, the factors involved in the contact pathway during aortic valve replacement were analyzed, and their impact on the development of thromboembolic complications was assessed. The results showed that TAVR or SAVR did not significantly activate the contact pathway. However, there was a significant reduction in FXI levels during the SAVR procedure, which was associated with a lower incidence of thrombotic events.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Javier Cuenca-Guardiola, Belen de la Morena-Barrio, Juan L. Garcia, Alba Sanchis-Juan, Javier Corral, Jesualdo T. Fernandez-Breis
Summary: Whole-genome sequencing using nanopore technologies can detect large structural variants with high accuracy. However, existing software for nanopore sequencing data analysis still has limitations in reporting complete and accurate variant sets, hindering molecular diagnosis and genotyping.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Medicine, Research & Experimental
Carlos Bravo-Perez, Mara Toderici, Joseph E. Chambers, Jose A. Martinez-Menarguez, Pedro Garrido-Rodriguez, Horacio Perez-Sanchez, Belen De La Morena-Barrio, Jose Padilla, Antonia Minano, Rosa Cifuentes-Riquelme, Vicente Vicente, Maria L. Lozano, Stefan J. Marciniak, Maria Eugenia de la Morena-Barrio, Javier Corral
Summary: This study characterized the biological and clinical impact of variants involving C-terminal antithrombin and found that the clinical phenotypes of these genetic changes are consistent with their dominant-negative effects.
Meeting Abstract
Hematology
Maria Luisa Lozano, Ana Zamora-Canovas, Belen De la Morena-Barrio, Cristina Sierra, Christoph Male, Jose Padilla, Maria Eugenia De la Morena-Barrio, Veronica Palma-Barqueros, Ana Sanchez-Fuentes, Agustin Rodriguez-Alen, Ana Marin-Quilez, Nuria Revilla Calvo, Vicente Vicente, Jose Maria Bastida, Javier Corral, Jose Rivera Pozo
Review
Surgery
Clara Gene Skrabec, Anna Vidal Carne, Manel Cremades Perez, Javier Corral, Andrea Fernandez Pujol, Marta Cuadrado, Jose Troya, Joan-Francesc Julian Ibanez, David Pares
Summary: The aim of this study was to review and assess the quality of scientific articles on early and late anastomotic leak (AL) after colorectal surgery and their risk factors. A systematic search was conducted using the MEDLINE database via PubMed, Cochrane, and Embase. The selected articles were reviewed and assessed for methodological quality using a validated methodology quality score (MINCIR score). The review was registered in the PROSPERO registry. Nine articles were finally reviewed, indicating the differentiation between early and late anastomotic leak based on technical factors and impaired healing.
Article
Biochemistry & Molecular Biology
Rosa Cifuentes, Jose Padilla, Maria Eugenia de la Morena-Barrio, Belen de la Morena-Barrio, Carlos Bravo-Perez, Pedro Garrido-Rodriguez, Maria Llamas, Antonia Minano, Vicente Vicente, Maria Luisa Lozano, Javier Corral
Summary: Multiplex ligation-dependent probe amplification (MLPA) is effective in identifying genetic structural variants in SERPINC1 in 5% of antithrombin deficiency (ATD) cases. However, MLPA has limitations in detecting intronic structural variants, and can produce imprecise and false-positive results for genetic defects affecting MLPA probes. Validation of MLPA results is encouraged based on our study.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Computer Science, Information Systems
Daniel Deniz, Gabriel Jimenez-Perera, Ricardo Nolasco, Javier Corral, Francisco Barranco
Summary: The pace of population ageing is increasing and becoming a significant challenge. The introduction of Cyber-Physical Systems (CPS) has facilitated the development of e-Health solutions for alleviating the associated burden. This study presents a CPS-based solution, a Deep Multimodal Habit Tracking system, to monitor and improve the autonomy and healthy lifestyles of individuals living alone at home. The system combines video and heart rate cues for accurate indoor action identification, with local processing ensuring data privacy and reducing bandwidth usage. The solution achieves high accuracy and additional heart rate information improves performance, especially in detecting critical actions like falls. The optimized model is embedded in a Nvidia Jetson Nano device, providing real-time performance with low power consumption. Additionally, a dataset specifically for indoor action recognition using synchronized video and heart rate pulses has been collected.
JOURNAL OF SIGNAL PROCESSING SYSTEMS FOR SIGNAL IMAGE AND VIDEO TECHNOLOGY
(2023)
Article
Hematology
Joanna Natorska, Javier Corral, Maria Eugenia de la Morena-Barrio, Carlos Bravo-Perez, Zsuzsa Bagoly, Zsuzsanna Bereczky, Jacek Trelinski, Michal Witkowski, Adrianna Klajmon, Anetta Undas, Michal Zabczyk
Summary: This study found that antithrombin deficiency increases the risk of thrombosis. It was discovered that antithrombin deficiency is associated with changes in fibrin clot permeability and lysis time.
THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Cardiac & Cardiovascular Systems
Ascension M. de los Reyes-Garcia, Laura Zapata-Martinez, Sonia Aguila, Maria L. Lozano, Constantino Martinez, Rocio Gonzalez-Conejero
Summary: Atrial fibrillation is a complex disease and microRNAs play a crucial role in the development of major adverse cardiovascular events (MACE) in these patients. MicroRNAs have been investigated as potential biomarkers for various diseases, including cardiovascular diseases. Some studies have associated certain microRNAs in plasma with the occurrence of MACE in atrial fibrillation. However, the lack of standardization in the purification and detection of microRNAs has produced contradictory results. Additionally, microRNAs have a functional impact on MACE in atrial fibrillation through the dysregulation of immunothrombosis, suggesting their potential use as therapy against thromboinflammatory processes.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Hematology
Belen de la Morena-Barrio, Angeles Palomo, Jose Padilla, Laura Martin-Fernandez, Juan Jose Rojo-Carrillo, Rosa Cifuentes, Carlos Bravo-Perez, Pedro Garrido-Rodriguez, Antonia Minand, Ana Maria Rubio, Javier Pagan, Maria Llamas, Vicente Vicente, Francisco Vidal, Maria Luisa Lozano, Javier Corral, Maria Eugenia de la Morena-Barrio
Summary: This study identified three structural variants affecting the F11 gene, which may have significant implications for the molecular pathology of congenital FXI deficiency.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Medicine, General & Internal
Jose Rayas, Mariam Hassan, Rivers A. Hock, Bryan Nguyen, Swathi Prakash, Adrian Rojas Murguia, Ilma Vahora, Javier Corral, Osvaldo Padilla, Fatma Dihowm
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a acquired X-linked, clonal hematopoietic stem cell disease with vague symptomatology, which poses difficulties in diagnosis, especially when coexisting with other hematologic disorders. The authors encourage screening for PNH clones in patients initially diagnosed with aplastic anemia (AA), treating underlying hematologic disease to prevent clonal expansion, and further research on the effectiveness of eculizumab in an unusual classical PNH secondary to AA with hypercellular bone marrow.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Medicine, General & Internal
Mariam Hassan, Swathi Prakash, Jose Rayas, Jared J. Bies, Sukhila Reddy, Sahithi Nadella, Sara Alhariri, Yousf Radwan, Nawar Hakim, Javier Corral
Summary: In this report, the authors present an unusual case of a 75-year-old female with a history of COVID-19 infection who developed transient ischemic attack, thrombocytopenia, and amegakaryocytopenia.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Medicine, Research & Experimental
David Zaragoza-Huesca, Maria Carmen Rodenas, Julia Penas-Martinez, Irene Pardo-Sanchez, Jorge Pena-Garcia, Salvador Espin, Guillermo Ricote, Andres Nieto, Francisco Garcia-Molina, Vicente Vicente, Maria Luisa Lozano, Alberto Carmona-Bayonas, Victoriano Mulero, Horacio Perez-Sanchez, Irene Martinez-Martinez
Summary: The research group identified a novel hepsin inhibitor, suramin, which can reduce invasion and thrombin generation of colorectal cancer cells. This study suggests the potential of repurposing suramin and its derivatives to enhance molecular targeted therapies against colorectal cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2023)