排序方式: 共有58条查询结果,搜索用时 31 毫秒
41.
Liu J Wang Y Yang Y Jiang X Zhao M Wang W Wu G Wu J Zheng M Peng S 《ChemMedChem》2011,6(12):2312-2322
Antifibrinolytic agents are required during complex surgeries to decrease bleeding; their pro-thrombotic potency and efficacy in causing hemostasis has attracted much attention. To discover new inhibitors of urokinase with high selectivity for antifibrinolytic effects over pro-thrombotic effects, the 12-position of (5aS,12S,14aS)- and (5aS,12R,14aS)-5,14-dioxo-1,2,3,5,5a,6,11, 12,14,14a-decahydro-5H,14H-pyrolo[1,2:4,5]pyrazino[1,2:1,6]pyrido[3,4-b]indoles were modified with L-Ala, L-Asp, L-Phe, L-Trp, L-Lys, L-Ser, Gly, and L-Leu to provide 16 (5aS,12S,14aS) and (5aS,12R,14aS) derivatives. In a murine bleeding model, the (5aS,12S,14aS) derivatives containing L-Ala, L-Asp, L-Phe, and L-Trp induced blood coagulation for the treated mice; they also stimulated thrombus formation in a rat thrombosis model, but the other derivatives inhibited thrombosis. The most potent compound, the L-Asp derivative, showed a good therapeutic window: the minimum effective dose for coagulation was <1 nmol kg(-1), whereas at 10 nmol kg(-1), no pro-thrombotic effect was observed. This type of coagulation action was correlated with a mechanism of urokinase inhibition, and these results could lead to the discovery of novel urokinase inhibitors. 相似文献
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Chunyan Cui Chuanchuan Fan Yuanhao Wu Meng Xiao Tengling Wu Dongfei Zhang Xinyu Chen Bo Liu Ziyang Xu Bo Qu Wenguang Liu 《Advanced materials (Deerfield Beach, Fla.)》2019,31(49)
Despite recent advance in bioinspired adhesives, achieving strong adhesion and sealing hemostasis in aqueous and blood environments is challenging. A hyperbranched polymer (HBP) with a hydrophobic backbone and hydrophilic adhesive catechol side branches is designed and synthesized based on Michael addition reaction of multi‐vinyl monomers with dopamine. It is demonstrated that upon contacting water, the hydrophobic chains self‐aggregate to form coacervates quickly, displacing water molecules on the adherent surface to trigger increased exposure of catechol groups and thus rapidly strong adhesion to diverse materials from low surface energy to high energy in various environments, such as deionized water, sea water, PBS, and a wide range of pH solutions (pH = 3 to 11) without use of any oxidant. Also, this HBP adhesive (HBPA) exhibits a robust adhesion to fractured bone, precluding the problem of mismatched surface energy and mechanical properties. The HBPA's adhesion is repeatable in a wet condition. Intriguingly, the HBPA is capable of gluing dissimilar materials with distinct properties. Importantly, introducing long alkylamine into this modular hyperbranched architecture contributes to formation of an injectable hemostatic sealant that can rapidly stop visceral bleeding, especially hemorrhage from deep wound. 相似文献
43.
Wen Yang Xinyi Kang Xu Gao Yan Zhuang Caixai Fan He Shen Yanyan Chen Jianwu Dai 《Advanced functional materials》2023,33(6):2211340
Bioadhesives have been used in clinics among the most prospective alternatives to sutures and staples for wound sealing and repairing; however, they generally have inadequate adhesion to wet surfaces, improper mechanical strength, poor hemostasis, and cytotoxicity. To address these challenges, a robust wet tissue adhesive based on collagen and starch materials (CoSt) is designed in this study. CoSt hydrogels integrate the feature of drainage, molecular penetration and strengthen cross-linking similar to mussel, ivy, and oyster glues, which remove interfacial water quickly, reinforce tough dissipation and involve multiple reversible dynamic interactions. Therefore, they form strong adhesion and sutureless sealing of injured tissues, accompanying actuate robust biointerfaces in direct contact with tissue liquids or blood, resolving the crucial impediments with sutures and commercially accessible adhesives. The novel bioadhesive shows repeatable strong wet tissue adhesiveness (62 ± 4.8 KPa), high sealing performance (153.2 ± 35.1 mmHg), fast self-healing ability, excellent injectability, and shape adaptability. For different hemostatic needs in rat models of tail amputation, skin incision, severe liver, abdominal aorta, and transected nerve injuries, the CoSt hydrogel shows better hemostatic efficiency than fibrin glue because of the coordinate efficacy of tough wound sealing property, outstanding red blood cell arresting capability, and the activation of hemostatic barrier membrane. Moreover, in vivo investigation of the skin injury repair of the rat model validate that CoSt hydrogels accelerate wound healing and functional recovery via skin damage/defects. Tough wet adhesion, quick hemostasis, distinguished biocompatibility, suitability to match irregular-shaped target sites, and good wound healing promotion of the CoSt hydrogel makes it a prospective bioadhesive for various biomedical applications. 相似文献
44.
Patricia A. Lozano Ahmed B. Alarabi Sarah E. Garcia Erica T. Boakye Hendreta T. Kingbong Elie Naddour Daniel Villalobos-García Precious Badejo Medhat S. El-Halawany Fadi T. Khasawneh Fatima Z. Alshbool 《International journal of molecular sciences》2022,23(5)
While cardiovascular disease (CVD) is the leading cause of death, major depressive disorder (MDD) is the primary cause of disability, affecting more than 300 million people worldwide. Interestingly, there is evidence that CVD is more prevalent in people with MDD. It is well established that neurotransmitters, namely serotonin and norepinephrine, are involved in the biochemical mechanisms of MDD, and consequently, drugs targeting serotonin-norepinephrine reuptake, such as duloxetine, are commonly prescribed for MDD. In this connection, serotonin and norepinephrine are also known to play critical roles in primary hemostasis. Based on these considerations, we investigated if duloxetine can be repurposed as an antiplatelet medication. Our results-using human and/or mouse platelets show that duloxetine dose-dependently inhibited agonist-induced platelet aggregation, compared to the vehicle control. Furthermore, it also blocked agonist-induced dense and α-granule secretion, integrin αIIbβ3 activation, phosphatidylserine expression, and clot retraction. Moreover duloxetine-treated mice had a significantly prolonged occlusion time. Finally, duloxetine was also found to impair hemostasis. Collectively, our data indicate that the antidepressant duloxetine, which is a serotonin-norepinephrine antagonist, exerts antiplatelet and thromboprotective effects and inhibits hemostasis. Consequently, duloxetine, or a rationally designed derivative, presents potential benefits in the context of CVD, including that associated with MDD. 相似文献
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46.
Grega Popovic Nicholas C. Kirby Taylor C. Dement Kristine M. Peterson Caroline E. Daub Heather A. Belcher Martin Guthold Adam R. Offenbacher Nathan E. Hudson 《International journal of molecular sciences》2022,23(3)
Fibrin forms the structural scaffold of blood clots and has great potential for biomaterial applications. Creating recombinant expression systems of fibrinogen, fibrin’s soluble precursor, would advance the ability to construct mutational libraries that would enable structure–function studies of fibrinogen and expand the utility of fibrin as a biomaterial. Despite these needs, recombinant fibrinogen expression systems, thus far, have relied on the time-consuming creation of stable cell lines. Here we present tests of a transient fibrinogen expression system that can rapidly generate yields of 8–12 mg/L using suspension HEK Expi293TM cells. We report results from two different plasmid systems encoding the fibrinogen cDNAs and two different transfection reagents. In addition, we describe a novel, affinity-based approach to purifying fibrinogen from complex media such as human plasma. We show that using a high-affinity peptide which mimics fibrin’s knob ‘A’ sequence enables the purification of 50–75% of fibrinogen present in plasma. Having robust expression and purification systems of fibrinogen will enable future studies of basic fibrin(ogen) biology, while paving the way for the ubiquitous use of fibrin as a biomaterial. 相似文献
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48.
Xin Peng Xiao Xu Yingrui Deng Xian Xie Limei Xu Xiayi Xu Weihao Yuan Boguang Yang Xuefeng Yang Xianfeng Xia Li Duan Liming Bian 《Advanced functional materials》2021,31(33):2102583
Achieving rapid and effective hemostasis on irregularly shaped, non-compressible visceral, and high-pressure arterial bleeding wounds remains a critical clinical challenge. Herein, an ultrafast self-gelling and wet adhesive polyethyleneimine/polyacrylic acid/quaternized chitosan (PEI/PAA/QCS) powder is reported as the hemostatic material and wound dressing. PEI/PAA/QCS powder deposited on bleeding wounds can rapidly absorb a large amount of blood to concentrate coagulation factors. Meanwhile, the powder can form an adhesive hydrogel in situ within 4 s upon hydration to form a pressure-resistant physical barrier. Furthermore, PEI/PAA/QCS hydrogels can aggregate blood cells and platelets to enhance hemostasis. Depositing PEI/PAA/QCS powder on various bleeding wounds, including at the liver and heart, high-pressure femoral artery and tail vein of rats, arrests the bleeding around 10 s with no rebleeding after ten minutes. Excellent hemostasis of PEI/PAA/QCS powder is further demonstrated against massive hemorrhage in porcine spleen and liver in vivo, which are non-compressible organs with abundant blood supply. In addition, the powder can be used as a wound dressing to promote the healing of the full-thickness skin wounds. The advantages of PEI/PAA/QCS powder including rapid and effective hemostasis, effective wound healing, easy usage, low cost, and adaptability to fit complex target sites make it a promising biomaterial for surgical applications. 相似文献
49.
Lin Teng Zhengwei Shao Qian Bai Xueliang Zhang Yu-Shi He Jiayu Lu Derong Zou Chuanliang Feng Chang-Ming Dong 《Advanced functional materials》2021,31(43):2105628
Despite clinical applications of the first-generation tissue adhesives and hemostats, the correlation among microstructure and hemostasis of hydrogels with wound healing is less understood and it is elusive to design high-performance hydrogels to meet worldwide growing demands in wound closure, hemostasis, and healing. Inspired by the microstructure of extracellular matrix and mussel-mimetic chemistry, two kinds of coordinated and covalent glycopolypeptide hydrogels are fabricated, which present tunable tissue adhesion strength (14.6–83.9 kPa) and microporous structure (8–18 µm), and lower hemolysis <1.5%. Remarkably, the microporous size mainly controls the hemostasis, and those hydrogels with larger pores of 16–18 µm achieve the fastest hemostasis of ≈14 s and the lowest blood loss of ≈6% than fibrin glue and others. Moreover, both biocompatibility and hemostasis affect wound healing performance, as assessed by hemolysis, cytotoxicity, subcutaneous implantation, and hemostasis and healing assays. Importantly, the glycopolypeptide hydrogel-treated rat-skin defect model achieves full wound closure and regenerates thick dermis and epidermis with some hair follicles on day 14. Consequently, this work not only establishes a versatile method for constructing glycopolypeptide hydrogels with tunable adhesion and microporous structure, fast hemostasis, and superior healing functions, but also discloses a useful rationale for designing high-performance hemostatic and healing hydrogels. 相似文献
50.
Yunlong Yu Pengfei Li Chenglei Zhu Ning Ning Shiyong Zhang G. Julius Vancso 《Advanced functional materials》2019,29(35)
A growth in the use of antibiotics and the related evolution of patients' drug resistance calls for an urgent response for the development of novel curing approaches without using synthetic antibiotics. Here, the fabrication of a low‐cost cryogel for wound dressing applications is demonstrated. The cryogel is composed of only naturally derived components, including chitosan/silk fibroin as the scaffold and tannic acid/ferric ion (TA/Fe3+) as the stimuli‐responsive agent for photothermal therapy. Based on the multiple weak hydrogen bonds and metal ligand coordination, the cryogel exhibits good flexibility and recoverability. Its highly porous structure renders the cryogel to be strongly hygroscopic to absorb blood for hemostasis. The cryogel exhibits excellent antibacterial activity to both Gram‐negative and positive bacteria, benefiting from the high photothermal transition activity of the TA/Fe3+ complex. Furthermore, the cryogel can efficiently promote cell proliferation in vitro. Significantly, animal experiments also reveal that the cryogel effectively eradicate microbes at the wound and accelerate the wound healing process. In summary, this novel biorenewable cryogel demonstrates excellent hygroscopic and hemostatic performance, photothermal antimicrobial activity, and accelerates skin regeneration, which has great application potential as a promising wound dressing material in the clinical use. 相似文献