Platelet-released polyphosphate controls thrombin generation.
Kurth Jack M JM, Zhang Xu X, Aslan Joseph E JE, McCarty Owen J T OJT
Shanghai RAAS Blood Products Co., Ltd. · F2 · 细胞治疗
thrombin 是一种细胞治疗,由Shanghai RAAS Blood Products Co., Ltd.研发。该药已获批,用于治疗相关适应症,给药途径:Oral (PO)。
| 商品名 | ThrombiRAAS |
| 公司 | Shanghai RAAS Blood Products Co., Ltd. |
| 药物类别 | 细胞治疗 |
| 分子靶点 | F2 |
| 给药途径 | Oral (PO) |
| 状态 | Approved |
thrombin 作用于 1 个分子靶点:
| F2 | coagulation factor II, thrombin (THPH1, PT) |
thrombin 针对 2 个适应症,涉及 1 个治疗领域。
| 治疗领域 | 疾病/病症 | 分期 |
|---|---|---|
| Vascular disorders | Extravasation blood | ✓ Approved |
| Vascular disorders | Haemorrhage | ✓ Approved |
Kurth Jack M JM, Zhang Xu X, Aslan Joseph E JE, McCarty Owen J T OJT
Nameny Arezoo A, DeSmet Austin A, Cai Can C, Baker Stephen R SR et al.
Low-density lipoprotein (LDL) is a major atherogenic lipoprotein, yet its potential to directly modify the fibrin scaffold of blood clots is incompletely understood. Here, we investigated how LDL alters plasma fibrin network architecture and internal fibrinolysis across defined fibrinogen/thrombin conditions. Pooled normal human plasma was supplemented with LDL and clotted with controlled concentrations of fibrinogen and thrombin. Fibrin architecture was visualized by confocal microscopy and quantified by pore-size analysis; clot formation and lysis were monitored turbidimetrically in the presence of tissue plasminogen activator (tPA). Increasing LDL produced a pronounced reduction in fibrin-network pore size across the tested fibrinogen/thrombin conditions. The LDL dependence of pore diameter was well described by a power-law relationship, D_pore = (6.54 ± 0.11)[ LDL ] -0.12 ± 0.02 , (R 2 = 0.90), with a significant negative LDL exponent (p = 4 × 10 -5 ). Increasing LDL also prolonged clot lysis time and altered turbidity kinetics. These findings extend epidemiologic and clinical associations between ApoB-containing lipoproteins and hypofibrinolytic clot phenotypes by demonstrating, in a controlled plasma system, that LDL itself can modify fibrin network architecture and fibrinolytic susceptibility. The results support a structure-function role for LDL within the fibrin biomaterial and motivate direct tests of LDL incorporation, protofibril packing, fibrinolytic-protein binding, and single-fiber mechanics.
Martins Jason J, Wirmer-Bartoschek Julia J, Schwalbe Harald H
Resolving the complex folding landscape of biomolecules contributes greatly to understanding cellular function, since cellular regulation and signal transduction are often linked to their conformational dynamics. We here investigate conformational transitions of a DNA deoxyguanosine G-quadruplex (G4) induced by binding of a low molecular weight azobenzene derivative. This ligand acts as a photoswitch that triggers conformational rearrangements of the thrombin binding aptamer (TBA) G4 in a reversible manner pending on the photoisomeric state of the ligand (E- or Z-configuration). We exploit the reversible association-dissociation of the photoactive ligand to extend current real-time NMR experiments, allowing the in-depth characterization of the folding pathways for the ligand association and dissociation processes and induction of G4 refolding. The folding pathway features kinetic partitioning and significant population of G4 folding intermediates.
Shara Khansa K, AlAjmi Hasan H, Baatiah Nada N, Darag Sara S et al.
Background and Clinical Significance: Refractory below-knee amputation (BKA) stump wounds can delay prosthetic rehabilitation. This report describes wound healing during multimodal care that included autologous platelet-rich plasma (PRP) activated with autologous thrombin serum (ATS); Case Presentation: A 33-year-old man with Charcot-Marie-Tooth disease and a persistent right BKA stump wound after surgical revisions underwent three PRP-ATS applications on 16 and 23 February and 8 March 2026. Collagen dressings were applied on 2 and 15 March, and compression was continued thereafter. The estimated wound volume decreased from 14.18 cm3 at baseline to 0.48 cm3 at week 3 (approximately 97%); advanced epithelialization was observed at week 4. Complete closure was documented on 16 April 2026, approximately eight weeks after treatment began. No treatment-related adverse events were reported. After closure, the patient was referred for prosthetic rehabilitation assessment; fitting and functional use were not documented; Conclusions: Healing was temporally associated with PRP-ATS as part of a multimodal treatment course. This single case supports the feasibility of the approach but cannot establish the independent efficacy of PRP-ATS.
Khodakarami Pardis P, Soltanolkottabi Fariba F, Jafari Hojat H
Leech saliva contains a diverse array of bioactive compounds, most notably hirudin, a potent natural thrombin inhibitor. Despite the clinical utility of hirudotherapy, inherent risks such as localized infection, uncontrolled hemorrhage, and leech migration limit its widespread application. To overcome these limitations, this study presents a refined extraction, partial purification, and stabilization protocol for hirudin-containing salivary extract derived from the Iranian leech, Hirudo orientalis. Saliva was harvested using 0.001 M arginine in 0.15 M saline under controlled temperatures (23 °C vs. 37-40 °C) and subsequently stored at 4 °C. The crude extract underwent fractionation/purification via centrifugation, followed by stabilization with sucrose, fructose, and mannitol, and final lyophilization (freeze-drying). Optimal extraction efficiency was observed at 37-40 °C. The short-term stability (44 days at 4 °C) and antibacterial efficacy of the resulting lyophilizate were evaluated using High-Performance Liquid Chromatography (HPLC) against authentic reference parameters and Brain Heart Infusion (BHI) broth assays. The findings demonstrate that this stabilization matrix preserves the short-term chromatographic profile and in-vitro biological activity of the salivary protein extract, providing a preliminary foundation for future in-vivo evaluation and development of standardized leech-derived biotherapeutics.
Folch-Puy Emma E, Llaves-López Andrea A, Barnat-Cabrera Queralt Q, Manso-Álvarez Paula P et al.
Endothelial dysfunction is a hallmark of numerous inflammatory and ischemic conditions, characterized by increased permeability, disruption of intercellular junctions and endothelial glycocalyx (eGCX) degradation. In the present study, we investigated the ability of polyethylene glycol 35 (PEG35) to preserve endothelial barrier integrity in cultured human umbilical vein endothelial cells (HUVECs) exposed to inflammatory, thrombotic, hypoxia-mimetic and eGCX-disrupting stimuli. PEG35 mitigated the loss of cellular metabolic activity induced by apoptotic and hypoxia-mimetic stress. Functionally, PEG35 attenuated stimulus-induced increases in FITC-dextran permeability and helped maintain trans-endothelial electrical resistance (TEER) under pro-inflammatory and eGCX-disrupting agents. PEG35 also reduced LDH release and maintained higher TEER values in endothelial cells exposed to plasma collected from pancreas transplant recipients after reperfusion, which contained increased circulating levels of the endothelial glycocalyx component syndecan-1. Mechanistically, PEG35 reduced NFĸB p65 nuclear translocation under thrombin, TNFα, and hyaluronidase stimulation and attenuated inflammatory and endothelial activation-related transcriptional responses. PEG35 also modulated intercellular junction gene expression in a stimulus and target-dependent manner, helped maintain occludin and claudin-5 protein expression under selected injurious conditions, and limited the loss of eGCX-associated syndecan-1 and heparan sulfate staining after enzymatic degradation. Collectively, these findings support a multifactorial endothelial-protective effect of PEG35 involving preservation of endothelial surface layer, maintenance of junctional integrity and attenuation of inflammatory signalling. These results identify PEG35 as a potential vasoprotective candidate for conditions involving acute endothelial barrier injury.
注册免费账户还可查看另外 9996 篇文献
免费注册查看全部文献 →