JOURNAL OF BIOMATERIALS APPLICATIONS
·
2024
·
IF 2.3
Bingru Zheng,Jinjie Chen,Yizhou Xu,Wanrui Wu,Yu Zhu,Wei Cai,Weili Lin,Changsheng Shi
Introduction: Deep vein thrombosis (DVT) is a major cause of cardiovascular disease-related deaths worldwide and is considered a thrombotic inflammatory disorder. IL-1β, as a key promoter of venous thrombus inflammation, is a potential target for DVT treatment. Constructing a nanocarrier system for intracellular delivery of siIL-1β to silence IL-1β may be an effective strategy for alleviating DVT. Methods: ELISA was used to detect the expression levels of IL-1β and t-PA in the serum of DVT patients and healthy individuals. In vitro, HUVEC cells were treated with IL-1β, and changes in VWF and t-PA expression levels were assessed. PBAE/MCM-41@siIL-1β (PM@siIL-1β) nano-complexes were synthesized, the characterization and biocompatibility of PM@siIL-1β were evaluated. A rat hind limb DVT model was established, and PM@siIL-1β was used to treat DVT rats. Morphology of the inferior vena cava, endothelial cell count, IL-1β, vWF, and t-PA levels, as well as changes in the p38 MAPK and NF-κB pathways, were examined in the different groups. Results: IL-1β and t-PA were highly expressed in DVT patients, and IL-1β treatment induced a decrease in VWF levels and an increase in t-PA levels in HUVEC cells. The synthesized PM@siIL-1β exhibited spherical shape, good stability, high encapsulation efficiency, and high drug loading capacity, with excellent biocompatibility. In the DVT model rats, the inferior vena cava was filled with blood clots, endothelial cells increased, IL-1β and VWF levels significantly increased, while t-PA levels were significantly downregulated. Treatment with PM@siIL-1β resulted in reduced thrombus formation, decreased endothelial cell count, and reversal of IL-1β, VWF, and t-PA levels. Furthermore, PM@siIL-1β treatment significantly inhibited p38 phosphorylation and upregulation of NF-κB expression in the DVT model group. Conclusion: IL-1β can be considered a therapeutic target for suppressing DVT inflammation. The synthesized PM@siIL-1β achieved efficient delivery and gene silencing of siIL-1β, demonstrating good therapeutic effects on rat hind limb DVT, including anti-thrombotic and anti-inflammatory effects, potentially mediated through the p38 MAPK and NF-κB pathways.
研究领域:
医学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
BIOMACROMOLECULES
·
2021
·
IF 6.988
Ronghua Yin,Lutan Zhou,Na Gao,Lisha Lin,Huifang Sun,Dingyuan Chen,Ying Cai,Zhili Zuo,Kaifeng Hu,Shengxiong Huang,Jikai Liu,Jinhua Zhao
Glycosaminoglycans (GAGs) are conserved polysaccharides composed of linear repeating disaccharides and play crucial roles in multiple biological processes in animal kingdom. However, saccharide-branched GAGs are rarely found, except the fucose-branched one from sea cucumbers. There was conjecture about the presence of disaccharide-branched GAG since 30 years ago, though not yet confirmed. Here, we report a GAG containing galactose-fucose branches from Thelenota ananas. This unique branch was confirmed as d-Gal4S(6S)-α1,2-l-Fuc3S by structural elucidation of oligosaccharides prepared from T. ananas GAG. Bioassays indicated that oligomers with a larger degree of polymerization exhibited a potent anticoagulation by targeting the intrinsic tenase. Heptasaccharide was proven as the minimum fragment retaining the anticoagulant potential and showed 92.6% inhibition of venous thrombosis in vivo at sc. of 8 mg/kg with no obvious bleeding risks. These results not only solve a long-standing question about the presence of disaccharide-branched GAG in Holothuroidea, but open up new opportunities to develop safer anticoagulants.
研究领域:
生物化学
·
海洋生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Dong Weichao,Li Huajian,Li Yanan,Wang Yuqing,Dai Long,Wang Shaoping
Background and aims: The increasing incidence of cardiovascular diseases has created an urgent need for safe and effective anti-thrombotic agents. Leech, as a traditional Chinese medicine, has the effect of promoting blood circulation and removing blood stasis, but its real material basis and mechanism of action for the treatment of diseases such as blood stasis and thrombosis have not been reported.Methods: In this study, Whitmania Pigra Whitman (WPW), Hirudo nipponica Whitman (HNW) and Whitmania acranutata Whitman (WAW) were hydrolyzed by biomimetic enzymatic hydrolysis to obtain the active peptides of WPW (APP), the active peptides of HNW (APH) and the active peptides of WAW (APA), respectively. Then their structures were characterized by sykam amino acid analyzer, fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectrometer and LC-MS. Next, the anti-thrombotic activities of APP, APH and APA were determined by carrageenan-induced tail vein thrombosis model in mice, and the anti-thrombotic mechanisms of high-dose APP group (HAPP), high-dose APH group (HAPH) and high-dose APA group (HAPA) were explored based on UHPLC-Q-Exactive Orbitrap mass spectrometry.Results: The results showed that the amino acid composition of APP, APH and APA was consistent, and the proportion of each amino acid was few different. The results of FT-IR and CD showed that there were no significant differences in the proportion of secondary structures (such as β-sheet and random coil) and infrared absorption peaks between APP, APH and APA. Mass spectrometry data showed that there were 43 common peptides in APP, APH and APA, indicating that the three have common material basis. APP, APH and APA could significantly inhibit platelet aggregation, reduce black-tail length, whole blood viscosity (WBV), plasma viscosity (PV), and Fibrinogen (FIB), and prolong coagulation time, including activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT). In addition, 24 metabolites were identified as potential biomarkers associated with thrombosis development. Among these, 19, 23, and 20 metabolites were significantly normalized after administration of HAPP, HAPH, and HAPA in the mice, respectively. Furthermore, the intervention mechanism of HAPP, HAPH and HAPA on tail vein thrombosis mainly involved in linoleic acid metabolism, primary bile acid biosynthesis and ether lipid metabolism.Conclusion: Our findings suggest that APP, APH and APA can exert their anti-blood stasis and anti-thrombotic activities by interfering with disordered metabolic pathways in vivo, and there is no significant difference in their efficacies.
研究领域:
中药学
·
分子生物学
·
代谢组学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Li Min,Han Bao,Fanqin Bu,Xueqing Li,Qingdong Guo,Mingyuan Liu,Shengtao Zhu,Jingxin Meng,Shutian Zhang,Shutao Wang
Venous thromboembolism (VTE) is the most fatal complication in cancer patients. Unfortunately, the frequent misdiagnosis of VTE owing to the lack of accurate and efficient evaluation approaches may cause belated medical intervention and even sudden death. Herein, we present a rapid, easily operable, highly specific, and highly sensitive procoagulant extracellular vesicle barcode (PEVB) assay composed of TiO2 nanoflower (TiNFs) for visually evaluating VTE risk in cancer patients. TiNFs demonstrate rapid label-free EV capture capability by the synergetic effect of TiO2-phospholipids molecular interactions and topological interactions between TiNFs and EVs. From ordinary plasma samples, the PEVB assay can evaluate potential VTE risk by integrating TiNFs-based EV capture and in situ EV procoagulant ability test with machine-learning-assisted clinical data analysis. We demonstrate the feasibility of this PEVB assay in VTE risk evaluation by screening 167 cancer patients, as well as the high specificity (97.1%) and high sensitivity (96.8%), fully exceeding the nonspecific and posterior traditional VTE test. Together, we proposed a TiNFs platform allowing for highly accurate and timely diagnosis of VTE in cancer patients.
研究领域:
医学诊断
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HISTOLOGY AND HISTOPATHOLOGY
·
2024
·
IF 2.5
Jinfeng Xie,Yonggui Liao,Dile Wang
Background: Deep vein thrombosis (DVT) is the third most prevalent vascular disease worldwide, seriously threatening human health. Baicalin, a flavonoid isolated from the roots of Scutellaria baicalensis , has been identified to play a crucial role in various vascular diseases. The study aimed to explore the efficacy and underlying mechanisms of baicalin in DVT. Methods: Endothelial progenitor cells (EPCs) were differentiated from peripheral blood mononuclear cells isolated from rat bone marrow. Dil-ac-LDL/FITC-UEA-1 double staining and flow cytometry analysis were conducted for the identification of EPCs. The angiogenesis and migration of EPCs in vitro were tested by a tube formation assay and Transwell assay, respectively. DVT rat models were established by stenosis of the inferior vena cava (IVC). After the euthanasia of rats, thrombi in the IVC were collected and weighed, and histological alterations in IVC tissue were measured by H&E staining. The protein levels of SIRT1, p-P65, and p65 in rat IVC tissues were quantified via western blotting. Results: EPCs used in this study displayed a spindle-like shape and were positive for endothelial cell-specific markers, suggesting the phenotypic characteristics of EPCs. Baicalin enhanced the migratory and angiogenetic abilities of EPCs in vitro . For in vivo experiments, baicalin reduced thrombus weight and mitigated DVT formation in model rats. Moreover, baicalin activated SIRT but repressed NF-κB signaling in IVC tissues of DVT rats. Conclusion: Baicalin facilitates migration and angiogenesis of EPCs but impedes thrombus formation via regulation of SIRT1/NF-κB signaling in DVT model rats.
研究领域:
药理学
·
血管生物学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2025
·
IF 4.8
Yu-Ming Huang,Cheng-Rang Liu,Yi-Qi Xu,Chao Cao,Zhen-Gan Huang,Hong-Wen Fei,Yue-Shan Huang
Objective: This study aimed to develop a poly (lactic-co-glycolic acid) (PLGA)-based magnetic loaded iron oxide (Fe3O4) and single-chain urokinase-type plasminogen activator (proUK) for enhancing thrombolysis under a controlled rotating magnetic field, specifically targeting acute lower limb venous thrombosis.Background: Acute thrombotic disorders are significant health threats, however, the exploration of magnetic actuation as a treatment for acute thrombosis has been limited.Methods: Magnetic microbubbles were prepared using a double emulsion method, loaded with Fe3O4 nanoparticles and proUK. The microbubble characteristics were analyzed through chemical, physical, and biological related technologies.Results: Fe3O4 nanoparticle loading was confirmed by X-ray diffraction, and the encapsulation efficiency of the magnetic microbubbles was determined using an ELISA kit and colorimetric assay, reaching a maximum of 56.65% at a proUK concentration of 7.5 mg/mL. Thrombolysis efficiency was significantly enhanced under a rotating magnetic field of 1.5 mT and 6 Hz frequency, achieving up to 25% lysis rate in vitro, markedly higher than control conditions. Furthermore, in vivo experiments using a rabbit model of hindlimb venous thrombosis validated the efficacy of this approach, with Color Doppler Flow Imaging showing restored blood flow and elevated D-dimer levels indicating effective thrombus dissolution.Conclusion: This novel magnetic drug delivery system, combined with a rotating magnetic field, demonstrates excellent thrombolysis efficiency and presents a promising and safe therapeutic strategy for acute venous thrombosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 10
·7195-7205
·
IF 3.9
Shun Xiao,Xiaozhi Sun,Chong Wang,Jianlie Wu,Kun Zhang,Mingjin Guo,Bing Liu
Deep vein thrombosis (DVT) is a venous return disorder caused by abnormal clotting of blood in deep veins. After thrombosis, most of the thrombus will spread to the deep vein trunk throughout the limb. If DVT is not treated in time, most of them will develop into thrombosis sequelae and even threaten life. Intravenous thrombolytic drugs are the most promising strategy for treating DVT, but current drugs used for thrombolysis suffer from short half-lives and narrow therapeutic indexes. To effectively manage DVT, it is necessary to develop a novel multifunctional drug-loading system to effectively prolong the treatment time and improve the therapeutic efficacy. In this study, a urokinase-loaded protocatechuic aldehyde-modified chitosan microsphere drug-loading platform was constructed for the treatment of DVT. This microsphere adsorbed urokinase well through electrostatic interaction, and the introduction of bovine serum albumin conferred stability to the microspheres. Therefore, the microsphere drug delivery system could achieve slow drug release to effectively dissolve blood fibrin. In addition, chitosan grafted with protocatechuic aldehyde imparted excellent antioxidant activity to the system to reduce free radicals in the blood vessels. Effective management of oxidative stress could avoid abnormal platelet activation and new thrombus formation. The experimental results showed that this microsphere had good biocompatibility, anti-inflammatory properties, and considerable thrombolytic activity. In conclusion, this study provided a new direction and developed a novel multi-functional nano microsphere drug delivery platform for the treatment of DVT.
研究领域:
药剂学
·
药理学
·
生物医学工程
·
材料科学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Research
·
2024
·
IF 8.5
Yaxin Ye,Zhechang Chen,Shengzhang Zhang,Paul Slezak,Fei Lu,Ruiqi Xie,Dongwon Lee,Guangqian Lan,Enling Hu
Thrombosis can cause life-threatening disorders. Unfortunately, current therapeutic methods for thrombosis using injecting thrombolytic medicines systemically resulted in unexpected bleeding complications. Moreover, the absence of practical imaging tools for thrombi raised dangers of undertreatment and overtreatment. This study develops a theranostic drug carrier, Pkr(IR-Ca/Pda-uPA)-cRGD, that enables real-time monitoring of the targeted thrombolytic process of deep vein thrombosis (DVT). Pkr(IR-Ca/Pda-uPA)-cRGD, which is prepared from a Pickering-emulsion-like system, encapsulates both near-infrared-II (NIR-II) contrast agent (IR-1048 dye, loading capacity: 28%) and urokinase plasminogen activators (uPAs, encapsulation efficiency: 89%), pioneering the loading of multiple drugs with contrasting hydrophilicity into one single-drug carrier. Upon intravenous injection, Pkr(IR-Ca/Pda-uPA)-cRGD considerably targets to thrombi selectively (targeting rate: 91%) and disintegrates in response to acidic thrombi to release IR-1048 dye and uPA for imaging and thrombolysis, respectively. Investigations indicate that Pkr(IR-Ca/Pda-uPA)-cRGD enabled real-time visualization of targeted thrombolysis using NIR-II imaging in DVT models, in which thrombi were eliminated (120 min after drug injection) without bleeding complications. This may be the first study using convenient NIR-II imaging for real-time visualization of targeted thrombolysis. It represents the precision medicine that enables rapid response to acquire instantaneous medical images and make necessary real-time adjustments to diagnostic and therapeutic protocols during treatment.
研究领域:
药学
·
生物医学工程
·
治疗诊断学
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Li Yan,Ge Jingping,Yin Yuanyuan,He Juan,Shang Longcheng
Background: This study aimed to explore the regulatory effect of anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying molecular mechanisms.Methods: Non-targeted metabolomics data analyses were conducted using an ultra-performance liquid chromatography system Vanquish UHPLC and mass spectrometer to detect plasma metabolism profiles. The transcriptome sequencing and gene intervention experiments were performed to verify the regulatory effect. Further in vivo and in vitro experiments were performed. Enzyme-linked immunosorbent assay was used to detect the levels of P-selectin, E-selectin, and vWF, hematoxylin-eosin (HE) staining was performed to observe thrombotic and inflammatory cell infiltration, flow cytometry and TUNEL assays were performed to detect apoptosis, and qPCR and WB assays were conducted to determine the gene and protein expression.Results: Anserine alleviated HUVECs injury, reduced adhesion molecule expression, and inflammation. It decreased P-selectin, E-selectin, vWF, THBD, TFPI levels, and apoptosis while promoting NOS3, ET-1, and NO release in HUVECs. In DVT rats, anserine reduced P-selectin, E-selectin, vWF, thrombosis, cell infiltration, apoptosis, and promoted NO release. Transcriptome sequencing and gene intervention confirmed anserine’s regulation of the PI3K-Akt pathway and coagulation via MYB. CARNMT1, a regulatory enzyme for anserine metabolism, increased anserine content, inhibiting coagulation, thrombosis, cell infiltration, and promoting NO release in rats.Conclusion: This study confirmed anserine could alleviate DVT by improving the inflammatory response, inhibiting blood agglutination, and promoting vasodilation, providing new potential therapeutic targets, important scientific evidence for the development of DVT management, and new clues for an in-depth understanding of its molecular mechanisms.
研究领域:
药理学
·
分子生物学
·
心血管疾病
·
血栓
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 41
·8659-8666
·
IF 6.331
Dan Fang,Ting Li,Ziyu Wu,Qi Wang,Mimi Wan,Min Zhou,Chun Mao
It is of great significance to find effective thrombolytic treatments due to the harm caused by thrombosis to human health. Based on the formation mechanism and complex microenvironment of a thrombus, polydopamine nanomotors (PDANMs) modified by the peptide of Arg–Gly–Asp (RGD) and loaded with urokinase (UK) were designed and prepared. A polydopamine (PDA) substrate has a good photothermal conversion effect. Under near-infrared (NIR) light irradiation, it can not only perform photothermal therapy (PTT) on thrombus, but also provide the driving force of PDANMs. Thrombolytic drug UK was loaded in the mesoporous structure of the PDA substrate and can be released at the thrombus site for drug therapy. The modified RGD can target the thrombus site, moreover, benefiting from the guanidine group of L-arginine in the peptide chain, and RGD can interact with reactive oxygen species (ROS) in the thrombus microenvironment to produce nitric oxide (NO). NO not only propelled the movement of nanomotors, but also promoted the growth of vascular endothelial cells to repair damaged blood vessels. The experimental results show that NIR and NO can provide dual driving sources for the nanosystem to achieve continuous and deep penetration of the drug-loaded nanomotors at the thrombus site, while realizing the photothermal and drug synergistic therapy to enhance the therapeutic effect and promote the growth of vascular endothelium cells. This kind of thrombus treatment strategy based on nanomotor drug delivery systems will provide good technical support for the clinical treatment of inferior vena cava thrombus.
研究领域:
生物医学工程
·
纳米技术
·
治疗学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 7
·946-952
·
IF 1.128
Mou Fengping,Xiao Li,Xu Yuanqin
This study aims to investigate the therapeutic effect of a paclitaxel-loaded nano-drug (PTX-mPEGPLA) on oral squamous cell carcinoma (OSCC). PTX-mPEG-PLA nanoparticle (NP) was prepared by loading paclitaxel into the mPEG-PLA nanoparticle and purified by a thin-film hydration method.
C57BL/6 mice were used to establish a murine OSCC model. The mice were treated with saline control (G1), paclitaxel (G2), or PTX-mPEG-PLA NPs (G3). After 4 weeks of differential treatment, the saliva of mice in the G1, G2, and G3 groups was collected to detect the concentration of protein
markers of OSCC. Also, venous blood and cancer tissues of mice in the three groups were collected for drug concentration measurements. The paclitaxel concentration and retention in G3 mice were significantly higher and more prolonged than those in G2 mice, respectively (P < 0.05).
Compared to the level of OSCC protein markers in the saliva of mice in G1 and G2 that in G3 was the lowest. PTX-mPEG-PLA NPs demonstrates effective targeting in the treatment of oral squamous cell carcinoma in mice. It can deliver the drug to the cancerous tissues, increase the drug retention
in the same tissues, and effectively inhibit the proliferation and metastasis of malignant tumors.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
实验医学
✓ 已验证
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2025
·Vol. 36
·期 1
·1-18
·
IF 4.5
Fang Cuifu,Duan Qing,Tang Ying,Fu Lifeng,Chen Juzheng,Zhou Weimin,Liu Fengen
Venous thromboembolism ranks as the third most prevalent cardiovascular disease. Nanotechnology-based drug carriers show significant potential for thrombolytic therapy. However, existing systems face challenges, including environmental impact and limited accessibility. To address these, we developed a novel delivery system using human black hair-derived nanoparticles (HNPs). These HNPs were loaded with the thrombolytic agent urokinase plasminogen activator (uPA) and a minimal concentration of gold nanoparticles (AuNPs). These components were encapsulated within a polyvinyl alcohol (PVA) membrane to create the nanocapsule drug delivery system, uPA-Au@HNP@PVA. Upon intravenous injection into a rat model with venous thrombosis, the system leveraged targeted blood flow to reach thrombus sites. Under 1064 nm NIR irradiation, the PVA membrane dissolved, exposing and releasing the drugs for intelligent thrombolysis. This system demonstrated excellent thrombolytic efficacy both in vivo and in vitro, coupled with robust biocompatibility in various biological tests, suggesting a wide range of potential applications. Graphical Representation: a. Depiction of the uPA-Au@HNP@PVA synthesis process. b. Diagrammatic explanation of intelligent thrombolytic therapy for specific drug delivery in a rat venous thrombosis model: I. Intravenous administration of uPA-Au@HNP@PVA; II. Targeted delivery to thrombus sites, navigation of uPA-Au@HNP@PVA to the thrombus location through targeted blood circulation, whereupon exposure to 1064 nm NIR irradiation causes a temperature rise, resulting in PVA dissolution, and drug release; III. NIR-triggered drug release and thrombolysis. Intelligent thrombolysis facilitated by 1064 nm NIR irradiation.
研究领域:
纳米技术
·
生物医学工程
·
心血管医学
·
药学
·
光响应治疗
✓ 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）