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
·
外科技术
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yun Li,Teng-Teng Ren,Shan-Shan Liu,Ling Zhang,Hong Yi,Chun Li,Liang-Mian Chen,Hui-Min Gao,Li-Hua Yan,Xiao-Qian Liu,Zhi-Min Wang
Ethnopharmacological relevance Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases ( Shang Han Lun ) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. Aim of the study The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. Materials and methods The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by “Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro . Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo . Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. Results The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1–S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro . Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 μg mL −1 ) in vivo . q-PCR data demonstrated that DGSN decoction (500 μg mL −1 ) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo . Conclusion The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.
研究领域:
中药学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF DERMATOLOGICAL RESEARCH
·
2025
·Vol. 317
·期 1
·1-8
·
IF 2.1
Ma Senlin,Sun Yuxin,Zhou Wenzhen,Yuan Yinuo,Yang Yifan,Zheng Yanchao,Lu Qiuxin,Chen Qingjiang,Ding Mingyue,Wang Guoyan,Chen Mingquan
Bullous pemphigoid (BP) represents an autoimmune blistering disorder that may coexist with acquired hemophilia A (AHA), a rare autoimmune condition arising from the formation of circulating autoantibodies directed against factor VIII (FVIII). The underlying pathomechanisms of BP-AHA remain elusive. This study conducted a retrospective analysis of data from 196 BP patients admitted to our hospital. We have collected serum samples from a recently admitted BP-AHA patient and healthy controls to isolate, screen and identify the potential FVIII inhibitors. The expression and function of lipopolysaccharide-binding protein (LBP) in BP-AHA were further validated by a series of biochemical experiments. The retrospective analysis showed that the activated partial thromboplastin time (APTT) values of seven patients exceeded 33.8 s (normal value) in 196 BP patients. FVIII: C (%) and FVIII inhibitors in the plasma of partial prolonged-APTT patients were significantly altered compared with control group or non-prolonged-APTT group. LBP was identified as a potential inhibitory protein of FVIII. Consistently, a notable alteration in LBP expression was observed in the plasma of BP patients with prolonged-APTT. Moreover, the amount of LBP bound to FVIII in the BP-AHA patient was notably higher than that in control group, which was also markedly reversed after treatment. In vitro experiments finally confirmed that exogenous LBP directly bound to FVIII and significantly inhibited FVIII activity. In conclusion, the incidence of AHA in BP patients may be substantially underestimated, which needs more vigilance towards indicators such as APTT, LBP, and FVIII. LBP emerges as an inhibitory protein of FVIII, indicating the potential involvement in the progression of BP-AHA.
研究领域:
免疫学
·
皮肤病学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 40
·8302-8314
·
IF 7.571
Yang Liu,Qiu Han,Guiliang Li,Haibo Lin,Fu Liu,Qiang Li,Gang Deng
Extracorporeal circulation (ECC) catheters have potential to be blood compatible and could be used to prevent thrombotic occlusion. Here, we produced heparin-mimicking anticoagulation PVC tubing on a large scale by synthesizing a heparin-mimicking polymer (HMP) and co-extruding. The PVC@HMP catheter was evaluated using whole human blood in vitro, which indicated it could prevent plasma protein attachment, reduce platelet adhesion and activation, and inhibit coagulation factors (XII, XI, IX, and VIII). Moreover, the anticoagulation PVC tubing was assembled into extracorporeal circulation with a New Zealand rabbit model, manifesting excellent real-time antithrombogenic properties without systemic heparin anticoagulation in vivo. The rapid recovery of coagulation factors after operation further confirmed its superiority over heparin, which would not completely inactivate the activity of those coagulation factors (XII, XI, IX and VIII). In addition, the PVC@HMP-1 catheters remain patent after being implanted in rats for 28 days without apparent inflammation and mortality complications. The anticoagulation PVC tubes could be used to construct various systemic and integrative anticlotting biomedical devices, which would dramatically reduce the introduction of heparin into blood circulation, thus preventing side effects and promoting the development of heparin-free treatment.
研究领域:
生物医学工程
·
血液学
·
材料科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2019
·
IF 3.532
Juan-Fang Lin,Lu-Lu Fan,Bo-Wen Li,Rui-Rui Zhao,Long-Guang Jiang,Bing-Chen Zhang,Yu-Sheng Lu,Jing-Wei Shao
Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.
研究领域:
药理学
·
心血管疾病
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2020
·
IF 7.242
Ying Wang,Xiaowen Xu,Xuan Zhao,Zongning Yin
Pathological thrombosis within a vessel hampers blood flow and is the mainspring of numerous fatal cardiovascular complications. In order to specifically image and dissolve a thrombus, we rationally designed a functionalized polymeric hybrid micelle (PHM) system self-assembled from amphiphilic polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethylene glycol (PCL-PEG). Based on a biological component of thrombi, activated coagulation factor XIII (FXIIIa), which is responsible for fibrin crosslinking, we further developed FXIIIa-targeted near infrared imaging and thrombolytic nanoparticles , termed IR780/FPHM/LK NPs, through chemical conjugation of peptides to the system. In a ferric chloride (FeCl 3 )-induced mouse carotid thrombosis model, IR780/FPHM/LK NPs specifically targeted the thrombus and significantly enhanced the photoacoustic signal for an accurate diagnosis. When loaded with the fibrinolytic drug lumbrokinase (LK), FPHM remarkably dissociated the thrombus accompanied by an increase in the d -dimer level, a fibrin degradation product , and alleviation of fatal nonspecific hemorrhagic risk. Given its thrombus-specific imaging along with potent therapeutic activities, IR780/FPHM/LK NPs hold promise for developing nanotheranostic agents in preclinical thrombotic vascular disease models.
研究领域:
纳米技术
·
诊疗学
·
心血管疾病
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Yule Wang,Huimin Wu,Hongda Sheng,Yingchao Wang,Xuecai Li,Yi Wang,Lu Zhao
Ischemic stroke is a leading cause of death worldwide, and it remains an urgent task to develop novel and alternative therapeutic strategies for the disease. We previously reported the positive effects of Guhong injection (GHI), composed of safflower extract and aceglutamide, in promoting functional recovery in ischemic stroke mice. However, the active substances and pharmacological mechanism of GHI is still elusive. Aiming to identify the active anti-stroke components in GHI, here we conducted a multi-phenotypic screening in zebrafish models of phenylhydrazine-induced thrombosis and ponatinib-induced cerebral ischemia. Peripheral and cerebral blood flow was quantified endogenously in erythrocytes fluorescence-labeled thrombosis fish, and baicalein and rutin were identified as major anti-thrombotic substances in GHI. Moreover, using a high-throughput video-tracking system, the effects of locomotion promotion of GHI and its main compounds were analyzed in cerebral ischemia model. Chlorogenic acid and gallic acid showed significant effects in preventing locomotor dyfunctions. Finally, GHI treatment greatly decreased the expression levels of coagulation factors F7 and F2, NF-κB and its mediated proinflammatory cytokines in the fish models. Molecular docking suggested strong affinities between baicalein and F7, and between active substances (baicalein, chlorogenic acid, gallic acid, and rutin) and NF-κB p65. In summary, our findings established a novel drug discovery method based on multi-phenotypic screening of zebrafish, provided endogenous evidences of GHI in preventing thrombus formation and promoting behavioral recovery after cerebral ischemia, and identified baicalein, rutin, chlorogenic acid, and gallic acid as active compounds in the management of ischemic stroke.
研究领域:
药理学
·
神经科学
·
药物发现
·
斑马鱼模型
·
中风研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Zhechang Chen,Caijie Yuan,Yaxin Ye,Bitao Lu,Enling Hu,Fei Lu,Kun Yu,Ruiqi Xie,Guangqian Lan
Arterial thrombosis is a critical thrombotic disease that poses a significant threat to human health. However, the existing clinical treatment of arterial thrombosis lacks effective targeting and precise drug release capability. In this study, we developed a system for targeted delivery and on-demand release in arterial thrombosis treatment. The carrier was constructed using chitosan (CS) and fucoidan (Fu) through layer-by-layer assembly, with subsequent surface modification using cRGD peptide. Upon encapsulation of urokinase-type plasminogen activator (uPA), the resulting therapeutic drug delivery system, uPA-CS/Fu@cRGD, demonstrated dual-targeting abilities towards P-selectin and αIIbβ3, as well as pH and platelet-responsive release properties. Importantly, we have demonstrated that the dual targeting effect exhibits higher targeting efficiency at shear rates simulating thrombosed arterial conditions (1800 s −1 ) compared to single targeting for the first time. In the mouse common iliac artery model, uPA-CS/Fu@cRGD exhibited great thrombolytic capability while promoting the down-regulation of coagulation factors (FXa and PAI-1) and inflammatory factors (TNF-α and IL-6), thus improving the thrombus microenvironment and exerting potential in preventing re-occlusion. Our dual-target and dual-responsive, fucoidan-based macrovesicle represent a promising platform for advanced drug target delivery applications, with potential to prevent coagulation tendencies as well as improving thrombolytic and reducing the risk of re-occlusion.
研究领域:
药学
·
生物医学工程
·
血栓研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2021
·Vol. 138
·期 46
·51360
·
IF 3.125
He Yang,Zhifang Ma,Xinghua Guan,Zehong Xiang,Yue Ke,Yu Xia,Zhirong Xin,Qiang Shi,Jinghua Yin
Excessive bleeding causes a large part of deaths in wars and accidents. It is necessary to prepare a hemostatic material with excellent performance and low cost through a facile strategy. Herein, the diatomite is modified with (3-Aminopropyl) triethoxysilane (APTES) to endow the aminated diatomite (ADia) with positive charge and interface compatibility with chitosan (CS) and sodium alginate (SA). Then, the facile fabrication of CS/SA/ADia sponge is successfully obtained by cross-linking with calcium ions. Compared to CS/SA sponge, the introduction of ADia further enhances the mechanical properties and hemostatic performance of CS/SA-based sponges. The composite sponges with 30 wt% ADia are demonstrated to possess high biocompatibility, compressive strength, water adsorption, and rapid hemostatic capability both in vitro and in vivo. The hemostatic performance is interpreted by activation of coagulation factors and platelets in intrinsic pathway, promotion of blood cell adhesion and formation of fibrin network. Our work provides an effective strategy to develop rapid hemostatic materials with low cost and high efficiency.
研究领域:
材料科学
·
生物医学工程
·
止血
·
生物相容性
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Yuting Shi,Wenwen Yu,Xiaoqin Liang,Ju Cheng,Yufei Cao,Mingsheng Liu,Yu Fang,Zheng Yang,Hongbin Liu,Hua Wei,Guanghui Zhao
Preventing arterial hemorrhage by intervening within the first few minutes is critical to the patient's life. Hemostatic materials have been developed over the last decades to address this issue, nevertheless these materials alone do not contribute to improve the survival effects in many extreme conditions, which is usually caused by penetrating arterial bleeding wounds that are incompressible and deep arterial bleeding with irregularly shapes. It is well known that, after calcium ion stimulation, many intriguing changes occurred in the major components of plasma, including the activation of several coagulation factors , such as the conversion of fibrinogen to fibrin, prothrombin to thrombin, and so on. Therefore, we constructed an expansion sponge with interpenetrating network based on chitosan and plasma, while various activated coagulation factors in plasma were also loaded into the pore structure of chitosan sponges. The prepared CS-PG sponge is capable of providing a simpler and more efficient method for treating high-pressure arterial bleeding wounds, which includes three steps: Rapid sealing and adhension, Thrombin catalysis and Activated autocoagulation. As the next generation bioactive materials , compared to conventional hemostatic materials, CS-PG sponge demonstrated superior hemostatic characteristics in both rabbit femoral artery damage and rat liver injury models.
研究领域:
生物材料
·
止血
·
伤口愈合
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Jiawen Chen,Liping Qiu,Qinglin Li,Jie Ai,Haiqing Liu,Qinhui Chen
It is important to control bleeding and prevent bacterial infection for the wound people. The effective way is to fabricate an asymmetric Janus matrial for realizing rapid hemostasis and promoting wound healing. Herein, mesoporous silica nanoparticles (MSN) modified by tannic acid (TA), silver nanoparticles, and calcium ions ( [email protected] ) with Janus structure were prepared via redox and coordination reactions. These anisotropic snowman-like particles possess obvious chemical compartition, in which silver nanoparticles are embedding in large MSN body. During blood coagulation, TA with catechol structure acts as a vasoconstrictor. Then, [email protected] with high specific surface area (510.62 m 2 ·g −1 ) and large pore volume (0.48 m 3 ·g −1 ) induces red blood cell aggregation to form three-dimensional network structure with fibrin. Additionally, calcium ions as clotting factor IV and negative charge of [email protected] accelerate coagulation cascade reaction. These three synergistic effects on animal model showed that hemostatic time of [email protected] was shortened by nearly 50% compared to that of MSN. Moreover, [email protected] possessed good blood compatibility, biocompatibility and antibacterial activity (~99%) against E. coli and S. aureus . The anisotropic Janus particles of [email protected] with hemostatic performance and antibacterial activity will be a promising biomaterial for designing wound dressings in clinical application.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
伤口护理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2022
·
IF 8.663
Caili LV,Xiaosong Zhou,Peng Wang,Zhenxu Wu,Zixue Jiao,Min Guo,Zongliang Wang,Yu Wang,Liqiang Wang,Peibiao Zhang
Broad interest in developing new commercial hemostatic agents has been widely aroused for massive blood loss in terms of hospital surgery and on the battlefield. In this study, we report biomimetic red-blood-cell like (RBC-like) hydrogel microspheres with controllable surface morphology by adjusting the proportion of carboxylated chitosan (CM) and gelatin (G) using Fe 3+ as crosslinking agent. It is worth noting that the microspheres are similar to RBCs in the dry state, with a microporous structure on the surface and a hollow structure inside, and enable restoration to the microsphere shape after absorbing water. The CMG1 microspheres show the best hemostatic effect, as indicated by whole blood coagulation in vitro and rat liver and leg artery damage models in vivo . The microspheres exhibit antibacterial properties against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). In addition, the microspheres have satisfactory degradation performance, hemocompatibility, biocompatibility and histocompatibility. This study indicates that these RBC-like microsphere-based hemostatic powders facilitate a physical barrier in wounds by forming aggregations. In addition, the micropores on the surface of the microspheres make it swell rapidly by absorbing blood, aggregating coagulation factors, activating platelets and ultimately accelerating the coagulation cascade to facilitate hemostasis. In conclusion, CMG1 hydrogel microspheres present potential application in the field of emergency hemostasis.
研究领域:
生物材料
·
止血
·
生物医学工程
·
伤口愈合
·
组织工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）