MOLECULES
·
2017
·Vol. 22
·期 12
·2047
·
IF 2.861
Xuan Luo,Chuanrong Du,Hui Cheng,Jian-hua Chen,Cuiwu Lin
In this study, three type II phenolic acids (caffeic acid,p-hydroxycinnamic acid, and ferulic acid) were used to synthesize a total of 18 phenolic acid derivatives. With molecular docking for molecule design and target protein (factors) screening, in combination with the confirmation of target proteins (factors) by surface plasmon resonance, and the evaluation of haemostatic and anticoagulant activities with five blood assays (plasma recalcification time, prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time), the data indicated that caffeic acid derivatives showed certain anticoagulant or procoagulant activities and that two other series contained compounds with the best anticoagulant activities. Using Materials Studio analysis, particular functional groups that affect anticoagulant or procoagulant activities were revealed, and these conclusions can guide the discovery of compounds with better activities.Keywords:anticoagulant;procoagulant;haemostatic;phenolic acid;surface plasmon resonance
研究领域:
生物学
·
医学
·
药理学
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DOI
PubMed
高影响因子
LAB ON A CHIP
·
2022
·Vol. 22
·期 4
·709-716
·
IF 7.517
Donghao Li,Xinyu Liu,Yujuan Chai,Jieying Shan,Yihan Xie,Yong Liang,Susu Huang,Weidong Zheng,Zida Li
The monitoring of coagulation function has great implications in many clinical settings. However, existing coagulation assays are simplex, sample-consuming, and slow in turnaround, making them less suitable for point-of-care testing. In this work, we developed a novel blood coagulation assay that simultaneously assesses both the tendency of clotting and the stiffness of the resultant clot using printed circuit board (PCB)-based digital microfluidics. A drop of blood was actuated to move back and forth on the PCB electrode array, until the motion winded down as the blood coagulated and became thicker. The velocity tracing and the deformation of the clot were calculated via image analysis to reflect the coagulation progression and the clot stiffness, respectively. We investigated the effect of different hardware and biochemical settings on the assay results. To validate the assay, we performed assays on blood samples with hypo- and hyper-coagulability, and the results confirmed the assay's capability in distinguishing different blood samples. We then examined the correlation between the measured metrics in our assays and standard coagulation assays, namely prothrombin time and fibrinogen level, and the high correlation supported the clinical relevance of our assay. We envision that this method would serve as a powerful point-of-care coagulation testing method.
研究领域:
医学工程
·
临床检验
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 98
·95358-95368
·
IF 3.289
Lingmei Lv,Fengling Tang,Guangqian Lan
The development of life-saving hemostatic materials for emergencies can reduce death caused by uncontrolled hemorrhaging. In this study, we developed a composite hemostatic material based on interactions between chitin and platelet-poor plasma (PPP) that promote in situ thrombin attachment to the chitin surface. Optimal conditions for preparing the chitin/PPP composite hemostatic material (CP), including reaction time, temperature, inducing ion, and thrombin concentration, were determined; thrombin activity and PPP clotting time were then measured under these conditions. We found that chitin and 2-fold-diluted PPP induced with 0.2 mol L−1 CaCl2 and reacted in a 35 °C water bath for 1 h yielded the fastest clotting time in vitro (75.0 ± 3.0 s). Furthermore, CP showed a more potent hemostatic effect than chitin in a rabbit model of arterial and hepatic bleeding, which was attributable to the strong adsorption of thrombin. The activated partial thromboplastin time revealed that CP promoted blood coagulation via activation of the endogenous coagulation pathway. CP caused no obvious cytotoxicity in L929 cells, and histopathological examination indicated that CP had no immunogenicity, and accelerated wound healing. These results highlight the potential for using CP as a hemostatic agent in clinical settings.
研究领域:
生物材料
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止血
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生物医学工程
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临床医学
✓ 已验证
DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-20
·
IF 16.6
Xu Tao,Ji Haifeng,Xu Lin,Cheng Shengjun,Liu Xianda,Li Yupei,Zhong Rui,Zhao Weifeng,Kizhakkedathu Jayachandran N.,Zhao Changsheng
Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.
研究领域:
血液学
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外科技术
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Chunchun Wang,Jiayi Guo,Qun Liu,Xu Zeng,Yue Liu,Yanping Deng,Yanli Lin,Xialing Wu,Hongju Deng,Linjing Chen,Wuyin Weng,Yucang Zhang
Accidental bleeding is an unavoidable problem in daily life. To avoid the risk of excessive blood loss, it is urgent to design a functional material that can quickly stop bleeding. In this study, an efficient wound dressing for hemostasis was investigated. Based on the characteristics that Ca 2+ and fish skin collagen (FSC) could activate the coagulation mechanism, hemostatic cotton was prepared by solvent replacement method using CaCl 2 , FSC, soluble starch (SS), and polyvinyl alcohol (PVA) as raw materials. The cytotoxicity test showed the Ca 2+ PVA/FSC-SS hemostatic cottons had good biocompatibility. The activated partial thromboplastin time (APTT) of Ca 2+ PVA/FSC-SS(4) was 35.34 s, which was 22.07 s faster than that of PVA/FSC-SS, indicating Ca 2+ PVA/FSC-SS mediated the endogenous coagulation system. In vitro coagulation test, Ca 2+ PVA/FSC-SS(4) could stop bleeding rapidly within 39.60 ± 5.16 s, and the ability of wound healing was higher than commercial product (Celox). This study developed a rapid procoagulant and hemostatic material, which had a promising application in a variety of environments.
研究领域:
生物材料
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止血
·
伤口愈合
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 116
·95710-95716
·
IF 3.84
Shuang-Shuang Fu,Jian-Ping Ning,Xiao-Hua Liao,Xiao Fu,Zheng-Bo Yang
Systemic anticoagulation is indispensable for hemodialysis patients to prevent clotting, but patients at high risk of bleeding cannot be given systemic anticoagulation. Hemodialyzer membrane modification maybe an effective program to solve this problem. In this study, we chose argatroban, a direct thrombin inhibitor, to modify a polyethersulfone (PES) membrane. Firstly, we prepared an argatroban (AG) grafted polyethersulfone (PES-AG) matrix by acetylating, oxidating and amidation reactions. Then, PES-AG was blended with PES at ratios of 2 : 1 and 1 : 1 respectively to prepare a PES/PES-AG membrane by using a phase inversion technique. FTIR and 1H NMR spectroscopy were used to confirm that argatroban was grafted to PES successfully. Scanning electron microscopy (SEM) was used to observe the characteristic morphology of the membranes. Activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and platelet function were detected to evaluate the antithrombotic property of the modified membrane. The results indicate that the antithrombotic property of the PES/PES-AG (1 : 1) membrane was superior to other three groups.
研究领域:
生物医学工程
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材料科学
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血液学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yuting Huang,Qianru Chen,Weijie Pan,Ying Zhang,Jiasheng Li,Xingyang Xue,Xinhe lei,Shumei Wang,Jiang Meng
Ethnopharmacological relevance As a traditional Chinese medicine , raw Moutan Cortex (RMC) has been used in clinical practice for thousands of years. However, its blood-cooling and blood-activating medicinal effects as well as the underlying mechanisms have not been preliminarily verified until recent years. Aim of the study Our group's previous network pharmacological studies suggested that RMC might exert its blood-activating and anti-inflammatory effects by modulating the coagulation-inflammation cascade pathway. Therefore, the present study aimed to further investigate the mechanisms relevant to the blood-activating and anti-inflammatory effects of RMC so as to provide more robust data supporting its clinical application. Materials and methods The inflammation and coagulation models of human umbilical vein endothelial cells (HUVECs) were induced by TNF-α; The rat models with blood-heat and blood-stasis syndrome (BHS) were constructed by ice-water bath with a combined use of epinephrine hydrochloride and dried yeast; The thrombus models of zebrafish were induced by arachidonic acid , and the inflammation models were established using LPS and CuSO 4 . The regulatory effects of RMC on the key targets in the pathway of the coagulation-inflammation cascade were investigated by combining ELISA , RT-PCR, and western blot techniques in an attempt to provide multiple validations concerning RMC's pharmacological efficacy and mechanism associated with cooling blood and activating blood circulation. Result The findings from the pharmacodynamic research demonstrated that RMC could inhibit the coagulation and inflammation process of HUVECs. Besides, it lowered the anal temperature and whole blood viscosity in BHS rats in addition to a prolongation of their prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT). Successfully constrained thrombotic area and reduced inflammatory cell counts were also observed in zebrafish models. Meanwhile, ELISA, RT-PCR and WB showed that RMC were capable of inhibiting the factors related to coagulation-MARK inflammation pathway—FⅡ, TF, FⅦ, FⅧ, FⅩ, and PAI, as well as down-regulating the expression of IL-6, COX-2, iNOS, TNF-α, ERK, JNK and p38. Conclusion RMC exerts blood-activating and anti-inflammatory effects through regulating the target genes of the coagulation-MARK inflammation cascade pathway.
研究领域:
民族药理学
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药理学
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中药
·
细胞生物学
·
动物模型
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2017
·
IF 4.95
Zhe Xu,Ruonan Liu,Huashi Guan
An accurate, rapid, and cost-effective methodology for enzyme assay is highly demanded to screen the effect of compounds on target at the molecular level. Thrombin (EC 3.4.21.5) and factor Xa (FXa, EC 3.4.21.6) have been identified as the critical targets for the development of potential drugs with anticoagulant activity. In this study, a rapid, sensitive and accurate assay based on UHPLC-MS/MS method has been developed for inhibitor screening against thrombin and factor Xa simultaneously. For thrombin and factor Xa, the Michaelis-Menten constants ( K m ) were calculated to be 6.14 and 57.27 μM, respectively. The inhibition constants ( K i ) for two known inhibitors, argatroban and rivaroxaban , were determined to be 16.23 and 0.41 nM, respectively. The assay was further validated through the determination of a high Z′ factor value of 0.89. Finally, the developed assay was applied to screen a chemical library against two enzymes . Three hit compounds belonging to a class of sulfated polysaccharides were identified and their targets of inhibition action were further evaluated. The results indicated that the dual-target assay by UHPLC-MS/MS analysis could be used as a reliable method for screening anticoagulant agents.
研究领域:
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 11
·6254-6266
·
IF 3.049
Ming-Ming Tu,Jing-Jie Xu,Yun-Ren Qiu
In this study, acrylic acid (AA) and sulfonated hydroxypropyl chitosan (SHPCS) were covalently grafted on the PSf membrane surface to improve its hemocompatibility. First, the modified AA-PSf membrane was obtained through the Friedel–Craft reaction between acrylic acid and the PSf membrane surface. Then, the modified SHPCS-AA-PSf membrane was prepared by grafting SHPCS onto the AA-PSf membrane surface via the dehydration acylation of the carboxyl group of the AA-PSf membrane with the amino group of SHPCS. ATR-FTIR and XPS measurements confirmed that the –COOH group and SHPCS were successfully grafted onto the surface of the PSf membrane. The modified PSf membranes showed suppressed platelet adhesion and lower protein adsorption (161 μg cm−2) compared with the pristine PSf membrane (341 μg cm−2). Hemocompatibility testing showed that modified membrane materials had a prolonged clotting time, plasma recalcification time (PRT), activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). All of these results indicated that the surface modification of the PSf membrane with acrylic acid and SHPCS had good hemocompatibility and anticoagulant property.
研究领域:
材料科学
·
生物材料
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Marine Drugs
·
2022
·Vol. 20
·期 10
·654
·
IF 6.085
Pathum Chandika,Pipuni Tennakoon,Tae-Hee Kim,Se-Chang Kim,Jae-Young Je,Jae-Il Kim,Bonggi Lee,BoMi Ryu,Hyun Wook Kang,Hyun-Woo Kim,Young-Mog Kim,Chang Su Kim,Il-Whan Choi,Won Sun Park,Myunggi Yi,Won-Kyo Jung
Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.Keywords:blood coagulation;anticoagulant;marine sources;marine anticoagulant macromolecules;chemically modified macromolecules
研究领域:
生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FIBERS AND POLYMERS
·
2023
·Vol. 24
·期 3
·801-810
·
IF 2.5
Wang Yi,Qin Hui,Chen Shuyi,Liu Yuan,Luo Jun,Nie Shengqiang
In this study, a highly efficient, convenient, and universal protocol of in situ cross-linking copolymerization of 2-hydroxyethyl methacrylate and sodium p-styrenesulfonate in polyvinylidene fluoride (PVDF) solution was presented to prepare blood-contacting material with good blood compatibility. The modified PVDF membranes were prepared by liquid–liquid-phase inversion technology, which could induce the enrichment of hydrophilic groups including sulfonic acid and hydroxyl groups on the surface of the modified PVDF membranes. The hydrophobic-fluorinated PVDF surfaces with hydrophilic sulphonic acid and hydroxyl groups exhibited high performance with prolonged clotting time (activated partial thromboplastin time and thrombin time) and low activation of blood components (platelets, coagulation cascade, and complements) when they contacted blood. On the other hand, the ultrafiltration experiment results revealed the improvement in the antifouling properties of the modified PVDF membranes after the introduction of hydrophilic groups on the membranes surface. The results indicate that the blood-compatible PVDF membranes may have potential to be used in the field of blood purification, and can be used as long-term blood-contacting materials as well.
研究领域:
材料科学
·
生物医学工程
·
血液相容性
·
膜技术
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Feng Wu,Yili Xu,Chenyang Ji,Xue Li,Jue Shen,Yejie Fei,Guanghan Yuan,Hui Qian
Background The coagulation process is inherently complex, and conventional diagnostic techniques are typically only capable of detecting single coagulation factors, lacking capacity to assess the overall coagulation function of the patient. Therefore, it is thus imperative to develop a novel, global coagulation assay for the diagnosis of hemorrhagic and thrombotic disorders and to evaluate the therapeutic efficacy of anticoagulant drugs. The ordered porous layer interferometry technology, developed using silica colloidal crystal (SCC) film as sensing substrate, is characterized by low cost, real-time, and convenient operation. Furthermore, entire biological events process can be detected by migration of the SCC film interference spectra. Results In this study, we developed a global coagulation assay with ordered porous layer interferometry by SCC film, a model of coagulation was created using fibrinogen and thrombin. The results demonstrated that this method could analyze the effect of different thrombin activities and different fibrinogen concentrations on the coagulation process. The performance of the coagulation assay was further validated using real blood samples and the method was found to have excellent detection capacity for different concentrations of CaCl 2 , which could trigger coagulation process. Hypercoagulable and hypocoagulable samples were tested by setting different biochemical conditions, and it could distinguish blood samples from different states significantly. Clinical samples were collected and the approach was compared with standard coagulation assays with satisfactory clinical correlation. Significance This global coagulation assay is simple, rapid and real-time, and does not require various biochemical reagents. The whole process of coagulation reaction can be recorded, and multiple coagulation indicators can be obtained in one test. It is anticipated to provide a novel low-cost and powerful method for clinical coagulation testing.
研究领域:
医学诊断
·
生物医学工程
✓ 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）