Research and Practice in Thrombosis and Haemostasis
·
2025
·
IF 3.4
Shunli Gu,Jinmei Xu,Erxiong Liu,Xuejia Hou,Ning An,Yaozhen Chen,Zhixin Liu,Wenting Wang,Xingbin Hu,Wen Yin
Background The timely administration of platelet transfusions is critical for patient survival, and the clinical demand for platelet transfusions has been steadily increasing. However, platelet storage lesion (PSL) that develops during in vitro preservation exacerbate these shortages. The PSL is significantly influenced by various factors, including temperature, gas composition, and buffering systems. Strategies to mitigate PSL and improve platelet storage have been actively explored in recent years. Objectives This study aimed to investigate whether elevated carbon dioxide (CO 2 ) levels improve platelet quality and functionality during storage. Methods Platelet concentrates from 28 donors were stored under control or 3% CO 2 conditions at 22 ± 2°C for up to 7 days. Platelet quality was evaluated through scanning electron microscopy, adhesion, aggregation, clot contraction, activation, apoptosis assays, blood gas, ATP, metabolomics analyses, and in vivo thrombosis and survival tests. Results Our findings indicate that increasing the CO 2 concentration in the storage environment mitigates PSL and improves platelet quality. Conclusions Our study highlights the potential benefits of utilizing a high-CO 2 storage environment to improve platelet preservation, offering a promising method to address clinical platelet shortages.
研究领域:
血液学
·
输血医学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RNA Biology
·
2021
·
IF 4.652
Yan Wang,Yujie Guo,Xiaolei Zhang,Hui Zhao,Bingbing Zhang,Yi Wu,Jingyu Zhang
Specific miRNA in immune thrombocytopenia (ITP) was screened to explore its intervention effects and mechanisms in ITP. MTT assay and CFSE staining were used to detect the effects of gradient concentrations of thrombopoietin (TPO) on cell proliferation. Expressions of differentially expressed miRNAs were analysed via qRT-PCR in TPO-induced megakaryocytes and ITP plasma. Effects of miR-557 on cell physiological functions were examined by MTT and flow cytometry. Expressions of miR-557, apoptosis-associated genes and Akt/ERK pathways were detected by qRT-PCR and Western blot as needed. Multinucleation of TPO-induced megakaryocytes was determined by megakaryocyte colonies. The toe skin and intestinal bleeding of the ITP rat model were observed and evaluated. Effects of miR-557 on the numbers of platelets, megakaryocytes, and peripheral blood platelets and the expressions of CD4+ T cells, Treg cells, TGF-β, IL-6 and miR-557 in the ITP rats were detected by Giemsa staining, flow cytometry, ELISA and qRT-PCR. MiR-557 was identified as an specific miRNA associated with both ITP and TPO treatment. MiR-557 inhibitor enhanced the physiological functions of TPO-induced megakaryocytes, while miR-557 mimic had the opposite effect. At the molecular level, the expressions of miR-557, cleaved Caspase-3 and Bax were further silenced by inhibitor, on the contrary, the expressions of bcl-2, p-Akt and p-ERK were upregulated. Animal experiments showed that, miR-557 inhibitor increased the numbers of platelets and megakaryocytes, and improved the symptoms of ITP model rats. Our results indicated that miR-557 inhibitor improved ITP by regulating apoptosis-related genes and cellular immunity and activating the Akt/ERK pathway.
研究领域:
血液学
·
分子生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Hematology
·
2025
·
IF 1.6
Yuying Chang,Yinglan Jin,Xi Chen,Xiaomin Zhang,Yaoyao Tian,Xinyu Gao,Xiushuai Dong,Wei Wang
Objective: This study aimed to investigate the effects of 4-Octyl itaconate (4-OI) on immune thrombocytopenia (ITP) mice model and elucidate the underlying mechanism.Methods: An ITP mouse model was established by intraperitoneal injection of the monoclonal antibody MWReg30 and treated by 4-OI with/without chloroquine (CQ). The mice were divided into four groups: Control, ITP, ITP+4-OI and ITP+4-OI + CQ. Platelet (PLT) content was detected and bone marrow megakaryocytes were quantified using Giemsa staining. Apoptosis was evaluated by TUNEL staining, protein expression of Bax and Bcl-2 in bone marrow tissues was detected by western blotting, and megakaryocyte apoptosis ratio was assessed by flow cytometry detection of CD61+ cells. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood, and the mRNA expression of LC3II, Becin-1, and SQSTM1 were detected by qRT-PCR; Immunofluorescence evaluated LC3II, Beclin-1, and SQSTM1 expression in bone marrow, as well as the ratios of CD41+Beclin-1+ and CD41+LC3II+ megakaryocytes.Results: Compared to the ITP group, 4-OI treatment significantly increased PLT counts, while reduced the spleen index and bone marrow megakaryocyte numbers. 4-OI also increased the apoptosis rate of megakaryocytes by increasing Bax protein expression and reducing Bcl-2 expression in the bone marrow. LC3II and Beclin-1 expression increased in PBMCs and bone marrow tissues, whereas SQSTM1 expression decreased. Megakaryocytes exhibited reduced LC3II and Beclin-1. The autophagy inhibitor chloroquine (CQ) suppressed all the 4-OI-induced effects.Conclusion: 4-OI ameliorated ITP-induced thrombocytopenia by modulating autophagy-related proteins in megakaryocytes, inducing autophagy, and promoting apoptosis.
研究领域:
免疫学
·
血液学
·
分子生物学
·
药理学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ELECTROPHORESIS
·
2015
·
IF 3.028
Feng-Qin Wang,Qian Zhang,Chun-Hong Li,Yin-Zhen Wang,Yuan-Jia Hu,Qi-Hui Zhang,Zhi-Ning Xia,Feng-Qing Yang
In this paper, an open tubular affinity capillary electrochromatography (OT-ACEC) was developed by physical adsorption of rabbit platelets on the inner surface of capillary. The interactions between small molecules include adenosine diphosphate (ADP) (positive control), protocatechuic acid (negative control) and seven natural products (salvianolic acid B, salvianic acid A sodium, hydroxysafflor yellow A, ferulic acid, chlorogenic acid, sinapic acid, caffeic acid) and platelets were evaluated by their retention factors and binding constants obtained based on peak-shift assay. Then, the activities of anti-platelet aggregation induced by thrombin (THR), ADP and arachidonic acid (AA) for those small molecules (except ADP) were evaluated by turbidimetric method. The results indicate that: (i) ADP, a platelet aggregation inducer, had strong interaction with platelet, while protocatechuic acid that had no inhibition on platelet aggregation behaved no specific interaction; (ii) there was a positive correlation between the anti-platelet aggregation activities of small molecules and their interactions with platelet, generally those compounds with higher binding constants with platelet exhibited higher activities. Therefore, the OT-ACEC method developed in the present study can be a potential method to evaluate affinity interactions between small molecules and platelets, so as to predict the biological activities such as anti-platelet aggregation for the small molecules.
研究领域:
药理学
·
分析化学
·
生物医学
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产品关联
DOI
PubMed
高影响因子
Science Translational Medicine
·
2022
·Vol. 14
·期 673
·
IF 19.319
Sisi Xie,Chenyu Jiang,Meng Wu,Ying Ye,Biying Wu,Xiaoting Sun,Xue Lv,Ruibo Chen,Wen Yu,Qi Sun,Yuting Wu,Rongliang Que,Huilan Li,Ling Yang,Wen Liu,Ji Zuo,Lasse D. Jensen,Guichun Huang,Yihai Cao,Yunlong Yang
Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet–induced circulating β-hydroxybutyrate (β-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-β-hydroxybutyrate dehydrogenase (BDH)–mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked β-OHB–induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body–MCT1–BDH–histone acetylation–platelet biogenesis axis in megakaryocytes and propose a nontoxic, low-cost dietary intervention for combating CIT.
研究领域:
医学
·
分子生物学
·
营养学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Xiao Fu,Ting Lei,Cong Chen,Gan Fu
The recent “cell-based theory” of coagulation suggests that platelets serve as the site of coagulation factor reactions, making platelets an effective target for inhibiting membrane thrombosis. Unfortunately, there is limited research on how blood purification membranes affect platelet intracellular signaling . In this study, we modified polyethersulfone (PES) membranes with the platelet phosphodiesterase (PDE) inhibitor dipyridamole (DIP) and investigated the effects of the DIP/PES (DP) membranes on platelet adhesion, activation, aggregation, and secretion, as well as the role of the PDE-cyclic adenosine monophosphate (cAMP) intracellular signaling pathway. Additionally, we evaluated the hemocompatibility and preliminary in vivo safety of DP membranes. Our results demonstrate that the modified DP membranes effectively inhibited platelet adhesion, membrane CD62P expression, and plasma soluble P-selectin activation levels. Furthermore, we confirmed that DP membranes achieved platelet aggregation inhibition and reduced platelet factor 4 and β-thromoglobulin secretion levels by inhibiting platelet intracellular PDE-cAMP signaling. Moreover, the modified DP membranes exhibited good anticoagulant and red blood cell membrane stability and complement resistance and demonstrated preliminary biocompatibility in mouse experiments. Collectively, these findings highlight the potential application of DP dialysis membranes in blood purification for critically ill patients.
研究领域:
血液学
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生物医学工程
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药理学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Guo Xi,Sun Tong,Zhong Rui,Ma Lu,You Chao,Tian Meng,Li Hao,Wang Chengwei
Chitosan oligosaccharide (COS) is known for its unique biological activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial activity, biological recognition, and immune enhancing effects, and thus continuous attracting many research interests in drug, food, cosmetics, biomaterials and tissue engineering fields. In comparison to its corresponding polymer, COS has much higher absorption profiles at the intestinal level, which results in permitting its quick access to the blood flow and potential contacting with blood components. However, the effects of COS on blood components remain unclear to date. Herein, two COS with different molecular weight (MW) were characterized by FTIR and 1H NMR, and then their effects on human blood components, including red blood cells (RBCs) (hemolysis, deformability, and aggregation), coagulation system [activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and the concentration of fibrinogen (Fib)], complement (C3a and C5a activation), and platelet (activation and aggregation), were comprehensively studied. In the case of RBCs, COS exhibited a low risk of hemolysis in a dose and molecular weight dependent manner and the irreversible aggregation was observed in their high concentration. For coagulation system, COS has a mild anticoagulation activity through blocking the intrinsic coagulation pathway. In addition, COS showed no effect on complement activation in C3a and C5a and on platelet activation while inhibition of platelet aggregation was evident. Finally, the mechanism that effects of COS on blood components was discussed and proposed.
研究领域:
医学
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生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Xiaoying Wang,Xiaoxing Fang,Xuewei Li,Hejiang Cheng,Hua Jiang,Ji Zheng
Tumor cell-platelet interaction is a critical pathway for promoting hematogenous metastasis by enhancing the survival rate of tumor cells. To establish a quantitative platform for evaluating cell interaction dynamics and drug interventions, we developed a novel porphyrin-based colorimetric system for real-time monitoring of tumor cell-platelet binding events. This detection system demonstrates excellent analytical performance, with a linear response range of 5.0 × 10 3 - 1.0 × 10 6 platelets and a limit of detection of 5.0 × 10 3 platelets. A comprehensive evaluation of lung adenocarcinoma cell lines revealed distinct platelet-binding capacities, with PC9R exhibiting the strongest platelet-binding ability, followed by A549, and PC9 showing the weakest ability. Moreover, we investigated the intervention of drugs and found that aspirin pretreatment could significantly reduce platelet binding in three cell lines. Among them, the inhibition of PC9R was most pronounced, followed by A549, and the weakest effect in PC9. The results indicate that drug pretreatment can significantly inhibit platelet binding in cell lines, and the inhibitory effect is positively correlated with platelet binding capacity-cells with stronger binding affinity show greater sensitivity to drug interventions. This study holds promise for analyzing the interaction between platelets and other cells, and may provide a basis for personalized selection of aspirin interventions.
研究领域:
癌症生物学
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血液学
·
生物化学
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-15
·
IF 7.5
Li Xingyu,Tang Zhaoxia,Kuang Liangjian,Wu Yongjian,Huang Xi
Background Platelets play a critical role in the pathophysiology of acute lung injury (ALI) by activating neutrophils and promoting the formation of neutrophil extracellular traps (NETs). Excessive NETs formation exacerbates lung injury by triggering inflammation, impairing essential alveolar macrophage functions and activating the coagulation cascade. Consequently, inhibiting NETs formation represents a promising strategy for treating ALI. Methods In this study, we developed platelet membrane-coated nanoparticles (PNPs) by encapsulating poly(lactic-co-glycolic acid, PLGA) nanoparticles within platelet membranes, and we characterized their physicochemical and functional properties. We investigated the effects of PNPs on platelet activation, NETs formation, mitochondrial ROS (mtROS) production and Syk phosphorylation in vitro. Furthermore, we evaluated the therapeutic effects of PNPs on acute lung inflammatory responses in a murine model. Results Compared with red blood cell membrane-coated nanoparticles (RBC-NPs), PNPs significantly inhibited both platelet activation and NETs formation. Mechanistic studies demonstrated that NETs generation was markedly attenuated via CD62P signaling inhibition in platelets and mitochondrial ROS scavenging in neutrophils (using mito-TEMPO), and these treatments exhibited a suppression efficiency that was comparable to that of PNPs treatment. In vivo experiments revealed that PNPs preferentially accumulated in the lungs of mice with ALI, reducing neutrophil infiltration and NETs formation. Furthermore, PNP treatment attenuated lung injury, as evidenced by reduced collagen deposition, decreased total protein levels and cell numbers in BALF, and decreased levels of proinflammatory cytokines in the lungs. Conclusions Our findings demonstrate that PNPs have potential for use in treating ALI by simultaneously attenuating platelet activation and NETs formation.
研究领域:
纳米医学
·
肺病学
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免疫学
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血液学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2018
·
IF 4.946
Xia Wang,QianQian Meng,XingRong Peng,GuiLin Hu,MingHua Qiu
Eight new ent -kaurane diterpene fatty acid esters, namely caffarolides A–H ( 1 – 8 ), were isolated from green beans of Coffea arabica . Their chemical structures were confirmed by extensive spectroscopic analysis including 1D, 2D NMR (HSQC, HMBC, 1 H– 1 H COSY, and ROESY), HRMS, IR and CD spectra and by GC-FID analysis. Interestingly, the diterpene moiety of these new compounds first occurred in genus Coffea . All the isolates were evaluated for platelet aggregation activity in vitro . As the results, caffarolides C, D and F ( 3 , 4 and 6 ) showed induction effect for platelet aggregation and the possible structure-activity relationships have been discussed briefly.
研究领域:
植物化学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-16
·
IF 12.6
Chu Hongyu,Xu Yajun,Shan Yuezhan,Sun Mengmeng,Zhao Weidong,Fang Xuedong,Shen Na,Tang Zhaohui
The vascular-disrupting agent DMXAA (5,6-dimethylxanthone-4-acetic acid) exhibits potent anticancer activity by targeting tumor vasculature and activating immune responses via the cGAS-STING pathway. However, its clinical application is hindered by nonspecific targeting and significant cardiovascular toxicity. This study introduces a novel self-amplified tumor-targeting delivery system(P@NPPD)comprising azide-functionalized poly(ethylene glycol)- b -poly-[( N -2-hydroxyethyl)-aspartamide]-DMXAA (N 3 -PEG- b -PHEA-DMXAA, NPPD) conjugated to DBCO modified platelets. Among them, NPPD was synthesized by conjugating DMXAA to N 3 -PEG- b -poly-[( N -2-hydroxyethyl)-aspartamide] through esterification. This system enhances tumor-specific drug delivery while minimizing systemic toxicity. Leveraging the natural tumor-homing properties of platelets and the coagulation cascade, P@NPPD selectively targets exposed collagen at tumor sites, initiating a self-amplifying release of DMXAA. This approach achieved a 2.61-fold improvement in targeting efficiency and an 89.1% tumor suppression rate. In addition to improving drug accumulation at tumor sites, P@NPPD significantly activated local immune responses, enhancing therapeutic efficacy and safety. These findings underscore the potential of P@NPPD as a promising platform for cancer therapy. Graphical abstract
研究领域:
药理学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2024
·Vol. 29
·期 9
·325
·
IF 3.3
Ziwei Guo,Sixu Bao,Zehui Shi,Xuejiao Li,Peijin Li,Bin Zhong,Ming Zhang,Qiyong Wu
Background: Platelets have the hemostatic function, and their aberrant activation is associated with occlusive thrombus formation. Plasma exosomes are rich in platelets containing ubiquitin-specific peptidase 15 (USP15). Herein, we aim to explore the effect of USP15 on thrombosis, as well as expounding whether USP15 acts as an upstream target of FK506 binding protein 5 (FKBP5) to regulate occlusive thrombus formation. Methods: Washed human platelets were treated with thrombin for measurement of USP15 and FKBP5 expressions. USP15 loss/gain-of-function variant in HEK293 cells was performed by cell transfection, and the interaction between USP15 and FKBP5 was examined using immunoprecipitation and ubiquitination assays. Mice with USP15-knockout platelets (Plt USP15-/-) were modeled, and subjected to calculation of bleeding time, artery thrombosis imaging and clot retraction assay. FKBP5 expression and the inhibitor of nuclear factor kappa B kinase subunit epsilon (IKBKE)/phosphatidylinositol 3-kinase (PI3K)/Rap1 pathway in wild-type and Plt USP15-/- mice-derived platelets were detected using Western blot. The activation of αIIbβ3 in washed platelets was analyzed using flow cytometry. Results: USP15 and FKBP5 expressions were upregulated in platelets after thrombin treatment. Following transfection of USP15 knockdown and USP15 overexpression plasmids into HEK293 cells, FKBP5 protein expression was downregulated by USP15 knockdown while being upregulated by USP15 overexpression. USP15 bound to FKBP5 and protected FKBP5 against ubiquitination. Knockdown of platelet USP15 prolonged bleeding time, inhibited arterial thrombosis and delayed clot retraction in mice. Knockdown of platelet USP15 also decreased protein expressions of FKBP5, IKBKE and Rap1, p-PI3K/PI3K ratio, and activation of αIIbβ3 in mice. Conclusion: USP15 knockdown in platelets affects thrombosis in mice by promoting the instability of FKBP5 to repress the activation of IKBKE/PI3K/Rap1 pathway-mediated αIIbβ3.
研究领域:
血液学
·
分子生物学
·
血栓
·
细胞信号传导
✓ 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）