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Marine Drugs · 2022 ·Vol. 20 ·期 10 ·654 · IF 6.085

Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants

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

CAS / MDL: 9012-76-4
研究领域: 生物学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF MEMBRANE SCIENCE · 2014 · IF 4.908

High efficient protocol for the modification of polyethersulfone membranes with anticoagulant and antifouling properties via in situ cross-linked copolymerization

Hui Qin,Chuangchao Sun,Chao He,Dongsheng Wang,Chong Cheng,Shengqiang Nie,Shudong Sun,Changsheng Zhao

In this paper, we provide a highly efficient, convenient and universal protocol for blood-compatible modification of polyethersulfone (PES) membranes via in situ cross-linked copolymerization of 2-hydroxyethl methacrylate (HEMA) and acrylic acid (AA) in PES solutions. Static water contact angle, protein adsorption, platelet adhesion, and clotting time of the modified PES membranes are systematically studied, and the results indicate that the modified membranes show improved hydrophilicity, good blood anticoagulant and antifouling properties after introducing HEMA and AA. Meanwhile, the modified membranes perform low contact activation and complement activation when they come in contact with blood. The effect of the HEMA/AA ratios on the blood compatibility is also investigated to identify the different roles played by HEMA and AA in the modification; the HEMA could more effectively enhance the membrane antifouling property, while the AA could more effectively improve the anticoagulant property. The results indicated that the blood-compatible PES membranes prepared via the in situ cross-linked copolymerization had potential to be used in the field of blood purification.

研究领域: 材料科学 · 生物医学工程
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MOLECULES · 2022 ·Vol. 27 ·期 9 ·3027 · IF 4.927

Physicochemical Properties and Anticoagulant Activity of Purified Heteropolysaccharides from Laminaria japonica

Tingting Li,Haiqiong Ma,Hong Li,Hao Tang,Jinwen Huang,Shiying Wei,Qingxia Yuan,Xiaohuo Shi,Chenghai Gao,Shunli Mi,Longyan Zhao,Shengping Zhong,Yonghong Liu

Laminaria japonicais widely consumed as a key food and medicine. Polysaccharides are one of the most plentiful constituents of this marine plant. In this study, several polysaccharide fractions with different charge numbers were obtained. Their physicochemical properties and anticoagulant activities were determined by chemical and instrumental methods. The chemical analysis showed thatLaminaria japonicapolysaccharides (LJPs) and the purified fractions LJP0, LJP04, LJP06, and LJP08 mainly consisted of mannose, glucuronic acid, galactose, and fucose in different mole ratios. LJP04 and LJP06 also contained minor amounts of xylose. The polysaccharide fractions eluted by higher concentration of NaCl solutions showed higher contents of uronic acid and sulfate group. Biological activity assays showed that LJPs LJP06 and LJP08 could obviously prolong the activated partial thromboplastin time (APTT), indicating that they had strong anticoagulant activity. Furthermore, we found that LJP06 exerted this activity by inhibiting intrinsic factor Xase with higher selectivity than other fractions, which may have negligible bleeding risk. The sulfate group may play an important role in the anticoagulant activity. In addition, the carboxyl group and surface morphology of these fractions may affect their anticoagulant activities. The results provide information for applications ofL. japonicapolysaccharides, especially LJP06 as anticoagulants in functional foods and therapeutic agents.Keywords:Laminaria japonica;polysaccharides;physicochemical properties;anticoagulant activity

研究领域: 海洋生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Marine Drugs · 2023 ·Vol. 21 ·期 3 ·148 · IF 5.4

Structural Elucidation of a Glucan from Trichaster palmiferus by Its Degraded Products and Preparation of Its Sulfated Derivative as an Anticoagulant

Haiqiong Ma,Qingxia Yuan,Hao Tang,Hongjie Tan,Tingting Li,Shiying Wei,Jinwen Huang,Yue Yao,Yaping Hu,Shengping Zhong,Yonghong Liu,Chenghai Gao,Longyan Zhao

Echinoderms have been attracting increasing attention for their polysaccharides, with unique chemical structure and enormous potential for preparing drugs to treat diseases. In this study, a glucan (TPG) was obtained from the brittle starTrichaster palmiferus. Its structure was elucidated by physicochemical analysis and by analyzing its low-molecular-weight products as degraded by mild acid hydrolysis. The TPG sulfate (TPGS) was prepared, and its anticoagulant activity was investigated for potential development of anticoagulants. Results showed that TPG consisted of a consecutive α1,4–linked D-glucopyranose (D-Glcp) backbone together with a α1,4–linked D-Glcpdisaccharide side chain linked through C-1 to C-6 of the main chain. The TPGS was successfully prepared with a degree of sulfation of 1.57. Anticoagulant activity results showed that TPGS significantly prolonged activated partial thromboplastin time, thrombin time, and prothrombin time. Furthermore, TPGS obviously inhibited intrinsic tenase, with an EC50value of 77.15 ng/mL, which was comparable with that of low-molecular-weight heparin (LMWH) (69.82 ng/mL). TPGS showed no AT-dependent anti-FIIa and anti-FXa activities. These results suggest that the sulfate group and sulfated disaccharide side chains play a crucial role in the anticoagulant activity of TPGS. These findings may provide some information for the development and utilization of brittle star resources.Keywords:brittle star;polysaccharide;glucan;structure;anticoagulant activity

研究领域: 海洋生物学 · 药学 · 生物化学
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2016 · IF 1.733

Poly(γ-glutamic acid), coagulation? Anticoagulation?

Tingting Xu,Fang Peng,Tao Zhang,Bo Chi,Hong Xu,Chun Mao,Shuaihui Feng

Poly(γ-glutamic acid) (γ-PGA) powder was usually used as hemostatic agent because of its excellent physical properties of water-absorption and water-locking. However, if γ-PGA absorbs enough water, how about its blood compatibility? Here, the other side of the coin was investigated. The anticoagulant properties of γ-PGA were characterized by in vitro coagulation tests, hemolytic assay, platelet adhesion, and platelet activation. Moreover, cytotoxicity experiments of γ-PGA were also carried out by MTT assay. Results indicated that the sufficient water-absorbed γ-PGA has good anticoagulant property and non-cytotoxicity. It means γ-PGA has good anticoagulant property, non-cytotoxicity. If γ-PGA has absorbed enough water, it can be used as an anticoagulation biomaterial. With double effects (coagulation and anticoagulation), the γ-PGA with desirable bioproperties can be readily tailored to cater to various biomedical applications.

CAS / MDL: 919-30-2
研究领域: 生物材料 · 止血 · 抗凝 · 生物相容性 · 生物医学工程
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Bioanalysis · 2024 · IF 1.9

The investigation of connection between anticoagulant therapy and vitamin K homologues in human determined by LC–MS/MS

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.

CAS / MDL: 67-56-1
研究领域: 医学 · 药理学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Multifunctional hyaluronic acid-based coating to direct vascular cell fate for enhanced vascular tissue healing

Yawen Zhao,Mingyu Li,Nuoya Chen,Kaiyang Huang,Xiaofeng Wu,Yanfei Tan,Qinsheng Hu,Rifang Luo,Yunbing Wang

Ensuring excellent anticoagulant, anti-inflammatory, and endothelialization properties in vascular stents through coating construction is crucial for their satisfactory performance post-implantation. In this study, we propose a cell-membrane mimetic multifunctional hyaluronic acid (HA)-based coating by combining the aminolyzed methacryloyloxyethyl phosphorylcholine (MPC) copolymer with oxidized hyaluronic acid (Ox-HA) through Schiff base reaction. Compared with traditional anti-fouling design, the composite coating present a stage-specific ability, which can resist the adhesion of blood components, while mediating vascular cell fate with the incorporation of HA. The coating exhibited promoted endothelial cell (EC) growth and inhibited the proliferation of smooth muscle cells (SMCs) by inducing a phenotype change. Besides, the multifunctional HA-based coating can mediate macrophages to a M2 phenotype. The coated stents were implanted in rabbits, and exhibited ideal capabilities in promoting endothelialization and inhibiting inflammation and restenosis in vivo , offering a potential approach to address multifunctionality for vascular implants.

研究领域: 生物医学工程 · 心血管医学
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ACS Biomaterials Science & Engineering · 2025 · IF 5.5

A New Type of Bioprosthetic Heart Valve: Synergistic Modification with Anticoagulant Polysaccharides and Anti-inflammatory Drugs

Xinyun Pu,Xu Peng,Shubin Shi,Shaoxiong Feng,Xu Wei,Xi Gao,Xixun Yu

Valvular heart disease (VHD) poses a significant threat to human health, and the transcatheter heart valve replacement (THVR) is the best treatment for severe VHD. Currently, the glutaraldehyde cross-linked commercial bioprosthetic heart valves (BHVs) remain the first choice for THVR. However, the cross-linking by glutaraldehyde exhibits several drawbacks, including calcification, inflammatory reactions, and difficult endothelialization, which limits the longevity and applicability of BHVs. In this study, λ-carrageenan with anticoagulant function was modified by carboxymethylation into carboxymethyl λ-carrageenan (CM-λC); subsequently, CM-λC was used as a cross-linking agent to stabilize decellularized bovine pericardial tissue through amide bonds formed by a 1-(3-(Dimethylamino)propyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide (EDC/NHS)-catalyzed reaction between the amino functional groups within pericardium and the carboxyl group located on CM-λC. Lastly, the inclusion complex (CD/Rutin) (formed by encapsulating the rutin molecule through the hydrophobic cavity of the mono-(6-ethylenediamine-6-deoxy)-β-cyclodextrin) was immobilized onto above BHVs materials (λCar-BP) through the amidation reaction. The treated sample exhibited mechanical properties and collagen stability similar to those of GA-BP, except for improved flexibility. Because of the presence of sulfonic acid groups and absence of aldehyde group as well as the Rutin release from CD/Rutin immobilized onto BHVs, the hemocompatibility, anti-inflammatory, HUVEC-cytocompatibility, and anticalcification properties, of the CM-λC-fixed BP modified with CD/Rutin was significantly better than that of GA-BP. In summary, this nonaldehyde-based natural polysaccharide cross-linking strategy utilizing the combination of CM-λC and CD/Rutin provides a novel solution to obtain BHVs with durable and stable anticoagulant, anticalcification, and anti-inflammatory properties, and has a wide range of potential applications in improving the various properties of BHVs.

研究领域: 医学材料学 · 心血管病学
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COMPOSITES PART B-ENGINEERING · 2023 · IF 13.1

Anti-fouling plus: Engineered stent coating with inflammation-regulation capability enables enhanced tissue healing

Hui Yan,Yumei Qin,Yanyan Li,Yongqi An,Haoshuang Wu,Chong Chen,Li Yang,Fanjun Zhang,Rifang Luo,Qing Jiang,Yunbing Wang

Coagulation, inflammation, and hyperplasia frequently restrict the effectiveness of cardiovascular stents . It is critical to modify stent surfaces to allow for in situ tissue healing. Interrelated coagulation and inflammation can impede endothelialization and are critical to the long-term performance of cardiovascular implants . This study proposes a relatively bio-inert “Anti-fouling plus” coating that is effective in anti-coagulation and anti-inflammation at the early stage of implantation and provides mild inflammatory responses during tissue remodeling process. The phosphorylcholine (PC)-based polymer PM(PCLA) is reacted onto a polydopamine-treated polylactic acid (PLA) surface. PC-based polymers that mimic cell membranes present remarkable antiinflammation and anticoagulation properties. The composite of epigallocatechin gallate (EGCG) and tempol is loaded on the PM(PCLA) coating to achieve “anti-fouling plus” which can mediate inflammatory responses by scavenging reactive oxygen species. In vitro hemocompatibility and cell tests demonstrate the effectiveness of coatings in inhibiting thrombus and inflammation. Interestingly, this study originally reveals a novel strategy that the anti-fouling plus coating can direct vascular tissue healing on stent via promoted endothelialization and mediated contractile smooth muscle cell phenotype by switching inflammatory cells to a pro-repair phenotype during tissue healing process, even if the coating is relatively bio-inert.

研究领域: 生物医学工程 · 心血管医学 · 材料科学
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Advanced Science · 2025 · IF 14.1

A Universal and Versatile Zwitterionic Coating for Blood-Contacting Catheters with Long Lengths and Complex Geometries

Tong Zhang,Tian Liang,Qichao Pan,Shouyan Zhang,Shuhua Zhang,Zhi Geng,Bo Zhu

Blood-contacting catheters are highly susceptible to thrombus formation, making heparin coating essential for reducing clinical complications. However, the limitations of heparin coatings have spurred significant efforts to develop alternative strategies. This study demonstrates a cost-efficient, mechanically viable, and universal zwitterion coating approach for long and complex catheters with near-zero fouling, super anticoagulation, and selective biocapturing. Leveraging the synergistic action of side groups, a wet-adhesive initiator-bearing polymer rapidly assembles on catheter surfaces in aqueous environments, facilitating the grafting of superhydrophilic and zwitterionic polymers onto catheter inner walls. This strategy demonstrates broad adaptability, successfully applying to ten substrates and showing exceptional versatility in modifying catheters and joints of various shapes and sizes. These coatings exhibit near-zero protein fouling across a broad pH range, and superior resistance to blood cells and bacteria. Furthermore, they maintain excellent stability under simulated bloodstream without compromising anticoagulant performance. Beyond antifouling properties, this method enables the construction of highly selective bio-interaction networks on catheter inner walls, allowing precise capture of circulating tumor cells from blood. This zwitterion coating technique, with its rapid modification, robust anticoagulant properties, and customizable bio-functionality, provides an attractive solution for, beyond catheters, a wide range of medical devices that must perform in challenging biological environments.

CAS / MDL: 111-30-8
研究领域: 生物医学工程 · 材料科学 · 血液学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2018 · IF 3.909

Characterization, sulfated modification and bioactivity of a novel polysaccharide from Millettia dielsiana

Zhonghua Wang,Tongqiang Cai,Xipu He

Millettia dielsiana is a traditional herb medicine to treat rheumatic arthritis and gynecological diseases. In this study, a novel polysaccharide (MDP1) with a molecular weight of 139.54 kDa was isolated from Millettia dielsiana by DEAE-52 cellulose chromatography. Its sulfated derivative (S-MDP1) was prepared by the chlorosulfonic acid-pyridine method. Structural analysis indicated that MDP1 was a pectic polysaccharide and did not exhibit a triple helical conformation. In vitro , MDP1 and S-MDP1 had protective effect on H 2 O 2 -induced PC12 cells death. Immunological assay showed that MDP1 and S-MDP1 significantly stimulated NO production and phagocytic activity in RAW264.7 cells, and promoted lymphocyte proliferation . Anticoagulant assay indicated that S-MDP1 effectively prolonged activated partial thromboplastin time (APTT) and thrombin time (TT), but not prothrombin time (PT), and MDP1 prolonged APTT and TT weakly. These results implied that MDP1 and S-MDP1 had the potential to be used as antioxidant, immunomodulatory and anticoagulant agents.

研究领域: 药理学 · 生物化学
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Research · 2022 · IF 11.036

Adhesive and Self-Healing Polyurethanes with Tunable Multifunctionality

Lei Zhou,Lu Zhang,Peichuang Li,Manfred F. Maitz,Kebing Wang,Tengda Shang,Sheng Dai,Yudie Fu,Yuancong Zhao,Zhilu Yang,Jin Wang,Xin Li

Many polyurethanes (PUs) are blood-contacting materials due to their good mechanical properties, fatigue resistance, cytocompatibility, biosafety, and relatively good hemocompatibility. Further functionalization of the PUs using chemical synthetic methods is especially attractive for expanding their applications. Herein, a series of catechol functionalized PU (C-PU-PTMEG) elastomers containing variable molecular weight of polytetramethylene ether glycol (PTMEG) soft segment are reported by stepwise polymerization and further introduction of catechol. Tailoring the molecular weight of PTMEG fragment enables a regulable catechol content, mobility of the chain segment, hydrogen bond and microphase separation of the C-PU-PTMEG elastomers, thus offering tunability of mechanical strength (such as breaking strength from 1.3 MPa to 5.7 MPa), adhesion, self-healing efficiency (from 14.9% to 96.7% within 2 hours), anticoagulant, antioxidation, anti-inflammatory properties and cellular growth behavior. As cardiovascular stent coatings, the C-PU-PTMEGs demonstrate enough flexibility to withstand deformation during the balloon dilation procedure. Of special importance is that the C-PU-PTMEG-coated surfaces show the ability to rapidly scavenge free radicals to maintain normal growth of endothelial cells, inhibit smooth muscle cell proliferation, mediate inflammatory response, and reduce thrombus formation. With the universality of surface adhesion and tunable multifunctionality, these novel C-PU-PTMEG elastomers should find potential usage in artificial heart valves and surface engineering of stents.

研究领域: 生物材料学 · 医学工程 · 心血管病学
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