Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression.

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

A erythrocyte-platelet hybrid membrane coated biomimetic nanosystem based on ginsenosides and PFH combined with ultrasound for targeted delivery in thrombus therapy.

Thrombus is one of the culprits for global health problems. However, most current antithrombotic drugs are limited by restricted targeting ability and a high risk of systemic bleeding. A hybrid cell membrane-coated biomimetic nanosystem (PM/RM@PLGA@P/R) was constructed in this paper to fulfil the targeted delivery of ginsenoside (Rg1) and perfluorohexane (PFH). Poly lactic-co-glycolic acid (PLGA) is used as carriers to coat Rg1 and PFH. Thanks to the camouflage of erythrocyte membrane (RM) and platelet membrane (PM), the nanosystem in question possesses remarkable features including immune escape and self-targeting. Therefore, a compact nano-core with PLGA@P/R was formed, with a hybrid membrane covering the surface of the core, forming a "core-shell" structure. With its "core-shell" structure, this nanoparticle fancifully combines the advantages of both PFH (the low-intensity focused ultrasound (LIFU)-responsive phase-change thrombolysis) and Rg1(the antioxidant, anti-inflammatory and anticoagulant abilities). Meanwhile, PM/RM@PLGA@P/R nanoparticles exhibits superior in-vitro performance in terms of ROS scavenging, anticoagulant activity and immune escape compared with those without cell membranes (PLGA@P/R). Furthermore, in the animal experiment in which the tail vein thrombosis model was established by injecting k-carrageenan, the combined treatment of LIFU and PM/RM@PLGA@P/R showed a satisfactory antithrombotic efficiency (88.20 %) and a relatively higher biological safety level. This strategy provides new insights into the development of more effective and safer targeted biomimetic nanomedicines for antithrombotic treatments, possessing potential application in synergistic therapy field.

The role of monocytes in thrombotic diseases: a review.

Cardiovascular and cerebrovascular diseases are the number one killer threatening people's life and health, among which cardiovascular thrombotic events are the most common. As the cause of particularly serious cardiovascular events, thrombosis can trigger fatal crises such as acute coronary syndrome (myocardial infarction and unstable angina), cerebral infarction and so on. Circulating monocytes are an important part of innate immunity. Their main physiological functions are phagocytosis, removal of injured and senescent cells and their debris, and development into macrophages and dendritic cells. At the same time, they also participate in the pathophysiological processes of pro-coagulation and anticoagulation. According to recent studies, monocytes have been found to play a significant role in thrombosis and thrombotic diseases of the immune system. In this manuscript, we review the relationship between monocyte subsets and cardiovascular thrombotic events and analyze the role of monocytes in arterial thrombosis and their involvement in intravenous thrombolysis. Finally, we summarize the mechanism and therapeutic regimen of monocyte and thrombosis in hypertension, antiphospholipid syndrome, atherosclerosis, rheumatic heart disease, lower extremity deep venous thrombosis, and diabetic nephropathy.

Simultaneous and sensitive detection of two pathogenic genes of thrombotic diseases using SPRi sensor with one-step fixation probe by a poly-adenine oligonucleotide approach.

Single-base mutations of Factor V Leiden G1691A and Prothrombin gene G20210A are the main genetic risk factors for inherited thrombotic tendency. The establishment for rapid and efficient detection method is of great significance to the prevention of venous thrombosis. In this work, a multiplexed, highly sensitive and regenerable surface plasmon resonance imaging (SPRi) sensor is described to identify and detect the two pathogenic genes by fixing probes in one-step. The probes are fixed by ployA, which is a simpler, faster and lower cost modification method compared with traditional thiol (-SH). PolyA-DNA-AuNPs is used to amplify the signal to improve sensitivity. The detection limit of the sensor is 8 pM, and it has a wide dynamic range between 8 pM and 100 nM and a good linear relationship between 8 pM to 50 pM. The equilibrium dissociation constant (KD) of 3.0 (± 0.3) pM indicates a high binding capacity. Based on the advantages of high-throughput detection, the SPRi chip can simultaneously identify and detect two genes related to thrombotic Diseases. In addition, more than 90% signal intensity can still be obtained on the surface of the chip after being regenerated of 25 times, indicating that this SPRi sensor has good stability and reproducibility. The established SPRi sensor has the advantages of high-throughput, high-sensitivity, label-free and no need for amplification, which is expected to become an effective technical means for real-time online detection of gene point mutations, and can be extended to detect and quantify a wider range of DNA mutation diseases.

Development and evaluation of thrombosis susceptibility gene chip / 吉林大学学报(医学版)

Objective: To explore the development methods and prelimnary clinical validation of thrombos susceptibility gene chip, and to illustrate a rapid and high-throughput method for detecting the thrombos susceptibility gene mutation. Methods: According to the published gene sequences of thrombotic susceptibility genes in GenBank, the reference probes and special probes were pointed on the glass slide. After ultraviolet crosslinking, thrombois susceptibility gene chip was eatablished. The validity of gene chip was tested by potive reference (mutant gene and normal gene at each detection site) and negative reference (distilled water) as templates, thereby performing PCR reaction. The specificity and sensitivity of gene chip were detected by using the human genome DNA of target sequence proven by sequencing as templates, thereby performng PCR reaction. Meanwhile 150 healthy subjects and 24 thrombosis patients with family hstory of unexplained thrombotic dsease from Jilin province, Henan provnce and Yunnan province were carried out the clinical verification of gene chip. The analyss index was the hybridization signal trength of the correspondng ite. Results: The hybridization results of postive reference and negative reference as templates showed that the specific hybridization signals appeared at the corresponding ites, which indicated that the detection sites of gene chip are effective. The gene chip used to detect the selected mutation sites had specific hybridization signals, suggesng there were good specificity of gene chip. The senstivity of gene chip was 50 - 100 mg · L-1 by testng genomic DNA with stepwise dilution. Eight individuals with thrombosis susceptibility gene mutations were found in 150 healthy subjects. Twenty ndividuals with thrombosis susceptibility gene mutations were found in 24 thrombosis patients with family hstory of unexplaned thrombotic dsease. The statistcs results showed that the detection rate of thrombosis susceptibility gene mutations in the thromboss patients with unexplaned thrombotic disease family history was significantly higher than that of the healthy subjects (P<0.05). Conclusion: The developed thrombosis susceptibility gene chip has great specificity, senstivity, and high detection rate of thromboss susceptibility genes. It has potental values in the early dagnosis and susceptibility sk assessment of thrombotic dseases.

Application of coagulation biomarkers in the diagnosis of thrombotic diseases in critically ill children / 中国小儿急救医学

Thrombotic diseases in children are much rare compared with adults,and the incidences are increasing in PICU during recent years.The characters of clinical presentations and the results of laboratory tests are different among various kinds of thrombotic diseases in children with venous thromboembolism,arterial thrombosis and thrombotic microangiopathy.The pathophysiological mechanism of thrombotic diseases comprise of coagulation activation and fibrinolysis suppression.Biomarkers of coagulation can reflect the early situation of coagulation and fibrinolysis.Fully and reasonably understanding the changes of various coagulation biomarkers in children is helpful for the early prediction and diagnosis of thrombotic disease.

Thromboelastography:clinical applications and new development / 国际检验医学杂志

Under normal physiological conditions, hemostatic process is a dynamic balance process dependent on many factors.It involves interaction between primary hemostasis (vasoconstriction, platelet clot formation), secondary hemostasis (thrombin generation, fibrin polymerization) and fibrinolysis, and any abnormalities of the three may cause hemorrhagic or thrombotic diseases.Conventional coagulation tests are useful for a limited degree since they only reflect a portion of the coagulation cascade.Thromboelastography (TEG) provides a more complete picture of coagulation status, taking into account more factors involved in the clotting process, including platelet activity and clotting factors, which has been widely used in clinic.In this article, we will briefly discuss clinical applications and new development of TEG.

In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking.

Coagulation Factor Xa (FXa) is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways. The inhibition of FXa is an effective approach against thrombotic diseases. In the present study, a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based (pharmacophore) virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules). The binding modes analysis provide insights into the contribution of particular structural moieties of the compounds towards their activity against FXa, and 10 novel structural compounds were discovered as potent candidate molecules. This work could be helpful in further design and development of FXa inhibitors.

Research advance in relationship between D-dimer and clinical diseases / 中国中西医结合急救杂志

D-dimer is widely used as a kind of coagulation index in clinics and commonly used in the judgement of thrombotic diseases. Recently, studies have found that the D-dimer is related to many clinical diseases in multiple systems, such as the inflammatory, tumorous, etc. diseases can all result in blood coagulation, inducing D-dimer elevation, which may have certain prediction effects on many clinical diseases in determining their diagnosis, prognosis and disease situations. This study has summarized the relationships of D-dimer with many clinical diseases.

Translational In Vivo Models for Cardiovascular Diseases.

Cardiovascular diseases are still the first leading cause of death and morbidity in developed countries. Experimental cardiology research and preclinical drug development in cardiology call for appropriate and especially clinically relevant in vitro and in vivo studies. The use of animal models has contributed to expand our knowledge and our understanding of the underlying mechanisms and accordingly provided new approaches focused on the improvement of diagnostic and treatment strategies of various cardiac pathologies.Numerous animal models in different species as well as in small and large animals have been developed to address cardiovascular complications, including heart failure, pulmonary hypertension, and thrombotic diseases. However, a perfect model of heart failure or other indications that reproduces every aspect of the natural disease does not exist. The complexity and heterogeneity of cardiac diseases plus the influence of genetic and environmental factors limit to mirror a particular disease with a single experimental model.Thus, drug development in the field of cardiology is not only very challenging but also inspiring; therefore animal models should be selected that reflect as best as possible the disease being investigated. Given the wide range of animal models, reflecting critical features of the human pathophysiology available nowadays increases the likelihood of the translation to the patients. Furthermore, this knowledge and the increase of the predictive value of preclinical models help us to find more efficient and reliable solutions as well as better and innovative treatment strategies for cardiovascular diseases.

Retrospective Analysis of Thromboembolism Prophylaxis in 115 Patients with Spinal Cord Injury / 中国康复理论与实践

Objective To retrospectively analyze the lower extremity deep vein thrombosis prevention in patients with spinal cord injury (SCI). Methods A total of 115 SCI patients in our department from April to May, 2015 were included. The clinical symptoms, lower limb deep vein ultrasonic testing, laboratory examination were collected to analyze the occurrence, prevention measures, the thrombus location and management of deep venous thrombosis (DVT) in lower limbs. Results Forty-three patients had thromboprophylaxis in other hospitals before admission, and 105 patients in our department after admission, in which, nine cases were with clinical symptoms in other hospitals and three cases in our department. No pulmonary embolism occurred in them. There was no significant difference in most laboratory index-es between patients with DVT and without DVT in lower limbs (P>0.05). Five patients were with DVT in lower limbs in 43 patients who had thromboprophylaxis, and four cases in 72 patients who did not have thromboprophylaxis. No relationship was found between thrombo-prophylaxis and DVT in lower limbs (χ2=0.663, P=0.415). Five patients were with DVT in lower limbs in 53 patients with complete SCI, and four cases in 59 patients with incomplete SCI. No relationship was found between the severity of SCI and DVT in lower limbs in other hospitals (χ2=0.028, P=0.867). Conclusion DVT in lower limbs could be also occurred in patients who accepted thromboprophylaxis. Labo-ratory indexes are inadequate for the prediction and diagnosis specificity of DVT in lower limbs.

Determination of D-dimer and its clinical application / 医学研究生学报

Plasma D-dimer is one of the degradation products of the cross-linked fibrin hydrolyzed by fibrinolysin and is also a unique metabolite of secondary fibrolysis.The change of its content is a reliable indicator for the identification of the hypercoagulabale state in vivo and primary and secondary fibrinolysis,as well as for the observation of the effectiveness of thrombolytic therapy.In recent years,D-dimer determination has gained new clinical application.

Effect of Hot-spring Bathing on the Control Factors of Coagulation / 日本温泉気候物理医学会雑誌

We have investigated change in platelets and the blood coagulation and fibrinolytic systems as a mechanism of the onset of thrombotic diseases during and after hot-spring bathing. In this study, We examined effect of 10min 42°C and 37°C hot-spring bathing on protein C, protein S and antithrombin III in seven healthy male subjects. The mean values of protein C antigen, protein C activity, total and fee protein S antigens, protein S activity and antithrombin III activity were slightly increased by both methods, while these changes were not statistically significant. Taken together with our previous reports, 10min 42°C hot-spring bathing gives no effect on the blood coagulation system.

Effect of Hot Spring Bathing on Nocturnal Blood Pressure at Kusatsu / 日本温泉気候物理医学会雑誌

The effect of hot spring bathing on nocturnal blood pressure was investigated in 6 normotensive young individuals at Kusatsu. Blood pressure and heart rate were measured at 1-hour intervals from 18:00 one day until 12:00 the following day. The experiments were performed on 2 consecutive days. Three subjects took a 10-minute 42°C hot-spring bath at 20:00 on the first experimental day but did not on the second experimental day. The order of experiments was inverted in the other 3 subjects. While not statistically significant, the nocturnal blood pressure on the “bathing” day tended to be decreased more than that on the control day. However, there was no difference in the heart rate. These findings may suggest possible involvement of hot spring bathing in the initiation of thrombotic diseases occurred in the morning hours at Kusatsu.