Bioanalysis
·
2024
·
IF 1.9
Xiemin Qi,Ning Chen,Qinxin Song,Yanan Chu,Haiping Wu,Jingwen Shan,Huijie Yue,Guohua Zhou
Aim: Differences are existed in the bioactivity among various vitamin K (VK) forms. To investigate the correlation between clinical parameters of initial anticoagulation and plasma levels of VK1 and VK2 (MK-4 and MK-7), it was necessary to establish a quantitative method for simultaneous determination.Materials & methods: Plasma samples in cardiovascular patients were extracted by cyclohexane and analyzed using a C18 column. Baseline concentrations of VK1, MK-4 and MK-7 were 0.98 ± 0.52 ng/ml, 0.45 ± 0.13 ng/ml and 0.65 ± 0.31 ng/ml, respectively. The concentrations of MK-7 and total VKs were significantly relevant to INR0, respectively (p = 0.010 and p = 0.048, respectively).Conclusion: Thus, when adjusting anticoagulation dosage, concentrations of various VK homologues might be considered.
研究领域:
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Mengfang Wu,Tian Xia,Yaran Li,Tianfa Wang,Shijia Yang,Jinchao Yu,Qiaoyan Liang,Teng Shen,Min Yu,Bing Zhao
Cardiovascular disease is the leading cause of global mortality, with anticoagulant therapy being the main prevention and treatment strategy. Recombinant hirudin (r-hirudin) is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous (SC) and intravenous (IV) administration, but there is a risk of haemorrhage via SC and IV. Thus, microneedle (MN) provides painless and sanitary alternatives to syringes and oral administration. However, the current technological process for the micro mould is complicated and expensive. The micro mould obtained via three-dimensional (3D) printing is expected to save time and cost, as well as provide a diverse range of MNs. Therefore, we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch. The results show that r-hirudin-loaded and hyaluronic acid (HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models. These results indicate that based on 3D printing technology, MNs combined with r-hirudin are expected to achieve diverse customizable MNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.
研究领域:
药剂学
·
生物医学工程
·
心血管疾病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xueping Tan,Dongnan Guo,Yujie Wang,Wenli Xu,Xiaofang Hou,Junbo Zhang,Sicen Wang
Factor XIa (FXIa), a pivotal target in anticoagulant therapy, requires precise activity monitoring to assess coagulation status and bleeding risks. To address the limited sensitivity of conventional chromogenic methods, we developed a novel electrochemiluminescence (ECL) biosensor exploring the synergistic effects of MXene's superior conductivity and Prussian blue analogue's (PBA) large specific surface area. Transient absorption spectrometry was employed to determine the excited-state lifetime and to elucidate the functional role of MXene@PBA. Molecular docking and specificity constant analysis identified Mpr(mercaptopropionic acid)-TEARK-Fc(ferrocene) as an optimal peptide substrate. The MXene@PBA-enhanced biosensor quantifies FXIa-induced ECL signal changes via peptide cleavage, achieving a linear range of 1.0 × 10 −5 mIU/mL to 1 mIU/mL and an LOD of 3.7 × 10 −6 mIU/mL (S/N = 3) in human serum. Furthermore, the ECL biosensor demonstrated efficacy in FXIa inhibitor screening, firstly revealing salvianolic acid A and C as potent inhibitors (>60 % inhibition) and apigenin as a moderate inhibitor (~40 %). Molecular docking confirmed that these inhibitors competitively bind to FXIa's catalytic pocket (His57, Cys58, Ala190, Lys192, Ser195), overlapping with the substrate recognition site. This MXene@PBA-enhanced ECL biosensor establishes a robust strategy for both FXIa activity monitoring and therapeutic agent development.
研究领域:
生物传感器
·
纳米材料
·
电化学
·
分析化学
·
分子生物学
·
药理学
·
抗凝治疗
·
表面科学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jun Liu,Yan Tang,Xiangyun Lin,Cheng Zhang,Nan Ma,Lei Wang,Wei Qu,Meiyu Shao,Yuxia Zhao,Wei Zhang
Thrombus formation associated with blood-contacting catheters remains a prevalent clinical issue. Antithrombotic coatings capable of inhibiting coagulation activation without interfering with hemostasis are highly desired. Herein, we constructed thick and densely packed poly(ε-acryloyl l-lysine) (p(LysAA)) zwitterionic brushes on the inner wall of chemical inert polyethylene (PE) catheters via a recently developed universal, substrate-independent coating strategy that enables facile scaling-up for catheters with complex geometries. The densely packed l-lysine-derived zwitterionic brushes exhibited ultrahydrophilic properties, with water contact angles below 10°. As expected, fouling by bovine serum albumin, fibrinogen, bacteria, platelets, and red blood cells was effectively suppressed. Moreover, the brushes demonstrated excellent biocompatibility, as evidenced by relative cell growth rates of over 90%, a hemolysis rate of below 1%, and intradermal reaction scores of less than 1.0. Importantly, it showed antithrombotic efficacy both in vitro and an in vivo. In a rabbit arterio-jugular vein shunt model, no obvious clotting was observed after 1 h of circulation. Overall, the brushes hold significant clinical potential in reducing the level of thrombus formation for blood-contacting catheters. Furthermore, by leveraging the abundant reactive amine and carboxyl groups within the p(LysAA) brushes, this approach provides a platform for integrating bioactive molecules to further mitigate the thrombotic risk.
研究领域:
生物医学工程
·
生物材料
·
表面科学
·
抗凝治疗
·
医疗器械
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Oushan Tang,Shitong Wang,Guanguan Qiu,Majun Zhang,Liping Ling,Yan Zhang,Meiqun Guo,Chunxia Shen,Bin Quan,Hongjie Lang,Qing Shen,Keyun Cheng
This study proposes a method combining the Captiva enhanced matrix removal (EMR)-Lipid solid-phase extraction column with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the qualitative and quantitative analysis of five common oral anticoagulants (OACs) (rivaroxaban, apixaban, edoxaban, dabigatran, and warfarin) in plasma samples. The method, through a simplified sample pretreatment, significantly enhances the recovery rate of OACs (ranging from 88% to 96%), demonstrating superior purification effects compared to traditional solid-phase extraction methods, and effectively removes matrix interference. The method exhibits good linearity over a concentration range of 0.010 to 5.0 × 10 2 ng·mL −1 (r 2 = 0.9514 to 0.9998), with high sensitivity, detection limits of 0.010 to 0.10 ng·mL −1 , and quantification limits of 0.10 to 1.0 ng·mL −1 . The recovery and precision analysis indicate that the method is highly accurate and stable, suitable for the analysis of large batches of plasma samples containing OACs. This method provides an efficient and reliable testing tool for clinical drug monitoring, contributing to the optimization and enhancement of safety in personalized anticoagulation therapy.
研究领域:
临床药理学
·
药物代谢
·
分析化学
·
个体化医学
·
毒理学
·
生物分析
·
抗凝治疗
✓ 已验证
产品关联
DOI
高影响因子
PHARMACOLOGICAL RESEARCH
·
2025
·
IF 10.5
Ning Yu,Shule Zhang,Rui Fang,Yingxin Zhang,Xi Xu,Lijuan Cao,Jianfa Zhang
Clinically approved thrombolytic agents carry significant bleeding risks due to systemic plasminogen activation. Heparin analogs prevent thrombus formation but lack direct thrombolytic activity. Here, we report a previously unrecognized thrombolytic mechanism of octaparin, a synthetic heparin analog. Studies demonstrated that octaparin exhibits potent anticoagulant and thrombolytic activity both in vitro and in vivo , with a lower bleeding risk compared to conventional heparin-based agents. Octaparin directly binds fibrin monomers, altering their secondary conformation to inhibit polymerization and destabilize preformed thrombi, while preserving tissue factor-driven coagulation. In murine models of pulmonary embolism and inferior vena cava thrombosis, octaparin both prevented and dose-dependently dissolved established clots without compromising hemostatic integrity, sharply contrasting with conventional thrombolytics that induce hemorrhage. Further analyses using molecular docking, microscale thermophoresis, and spectroscopy confirmed that octaparin induces changes in fibrin monomer folding that compromise fibrin network stability. In human systems, octaparin selectively prolonged intrinsic coagulation time, reduced clot retraction, did not induce platelet activation, and its effects were reversible with protamine sulfate. This study establishes targeted fibrin destabilization as a viable therapeutic strategy, revealing a previously unrecognized thrombolytic mechanism achievable through heparin-based molecular design.
研究领域:
药理学
·
血液学
·
分子医学
·
血管生物学
·
抗凝治疗
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）