Chemokine CC-motif ligand 2 participates in platelet function and arterial thrombosis by regulating PKCα-P38MAPK-HSP27 pathway

Background

Studies indicate that chemokine CC-motif ligand 2 (CCL2) is involved in inflammation and atherosclerosis. However, the roles and mechanisms of CCL2 on platelet function and arterial thrombosis are unknown.

Design,synthesis and biological evaluation of anthranilamide derivatives as potential factor Xa (fXa) inhibitors

Factor Xa (fXa) is a crucial player in various thromboembolic disorders. Inhibition of fXa can provide safe and effective antithrombotic effects. In this study, a series of anthranilamide compounds were designed by utilizing structure-based design strategies. Optimization at P1 and P4 groups led to the discovery of compound 16g: a highly potent, selective fXa inhibitor with pronounced in vitro anticoagulant activity. Moreover, 16g also displayed excellent in vivo antithrombotic activity in the rat venous thrombosis (VT) and arteriovenous shunt (AV-SHUNT) models. The bleeding risk evaluation showed that 16g had a safer profile than that of betrixaban at 1?mg/kg and 5?mg/kg dose. Additionally, 16g also exhibited satisfactory PK profiles. Eventually, 16g was selected to investigate its effect on hypoxia-reoxygenation- induced H9C2 cell viability. MTT results showed that H9C2 cell viability can be remarkably alleviated by 16g.     

清栓酶治疗儿童脑动脉炎和脑血栓形成31例

用清栓酶治疗儿童脑动脉炎和脑血栓形成３１例,其中急性期２２例、恢复期５例、后遗症期４例,有效率分别为９Ｏ．９％、８０．０％和８７．１％．总有效率为８７．１％。脑动脉炎可导致血小板聚集性增高、血管闭塞和血栓形成,清栓酶可降低血小板聚集性,具有扩张血管,溶解血栓之作用,故可以使临床表现得以好转。     

蕲蛇酶对大白鼠和家兔实验性脑血栓的溶栓作用

采用血小板聚集诱导剂二磷酸腺苷（ＡＤＰ）加肾上腺素（Ａｄ）从家兔颈内动脉或大白鼠颈总动脉注入,以形成脑血栓,２ｈ后各组动物分别从静脉给予不同剂量蕲蛇酶（１５０、３００和６００ｍｇ／ｋｇ）,阳性对照药潘生丁（１０ｍｇ／ｋｇ）及空白对照生理盐水（１ｍｌ／ｋｇ）。以脑组织对伊文思蓝通透性改变及脑组织切片计算血栓数目为指标,判断蕲蛇酶对血栓的影响。结果不同剂量蕲蛇酶组对大鼠或家兔的实验性脑血栓均比生理盐水组血栓消褪加快,形成的血栓数目减少,脑组织伊文思蓝含量亦明显减少;潘生丁组亦显示促血栓消褪的效果     

Xylarinase: a novel clot busting enzyme from an endophytic fungus Xylaria curta

Xylarinase is a bi-functional fibrinolytic metalloprotease isolated from the culture filtrate of endophytic fungus Xylaria curta which is monomeric with a molecular mass of ～33.76?kDa. The enzyme displayed both plasmin and tissue plasminogen activator like activity under in vitro conditions. It hydrolyses Aα and Bβ chains of the fibrinogen. Optimal fibrinolytic activity of xylarinase is observed at 35?°C, pH 8. Ca²⁺ stimulated the fibrinolytic activity of xylarinase while Fe²⁺ and Zn²⁺ inhibited suggesting it to be a metalloprotease. The K_m and V_max values of xylarinase were 240.9?μM and 1.10?U/ml for fibrinogen and 246?μM and 1.22?U/ml for fibrin, respectively. Xylarinase was found to prolong the activated partial thromboplastin time and prothrombin time. The N-terminal sequence of xylarinase (SNGPLPGGVVWAG) did not show any homology with previously known fibrinolytic enzymes. Thus xylarinase is a novel fibrinolytic metalloprotease which could be possibly used as a new clot busting enzyme.     

来那度胺致多发性骨髓瘤患者静脉血栓形成的机制

来那度胺是一种新型的免疫调节药物,已被广泛应用于治疗多发性骨髓瘤,但其所致静脉血栓形成的副作用也越来越明显。当单独使用来那度胺治疗多发性骨髓瘤时,患者静脉血栓的发生率比较低,而其与地塞米松、化疗药物等联合使用治疗多发性骨髓瘤时,静脉血栓的发生率明显高于单独使用。来那度胺致多发性骨髓瘤患者静脉血栓形成的机制目前尚未完全阐明,国内外研究显示,其主要与内皮细胞功能紊乱、组织因子与磷脂酰丝氨酸暴露增加及体内的高凝状态相关。本文主要就来那度胺致多发性骨髓瘤患者静脉血栓形成的机制进行了简要综述。     

Therapeutics for advanced hepatocellular carcinoma: Recent advances,current dilemma,and future directions

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a serious threat to people's health worldwide. The prognosis of advanced HCC is dim if left untreated. In the clinic, the treatment options for advanced HCC include surgery, radiotherapy, transcatheter arterial chemoembolization, and so forth. In recent years, molecular targeted therapy and immunotherapy have also made great progress, bringing new hope to patients with advanced HCC. In this study, therapeutic advances, current dilemma, and future directions of advanced HCC are reviewed, which might serve as a summary for clinicians and may stimulate future research.     

Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis

Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.     

Erythrocyte hyperaggregation in obesity: determining factors and weight loss influence

Objective: To compare erythrocyte aggregation (EA) in patients with severe obesity without other cardiovascular risk factors with a control group, using the Myrenne and the Sefam aggregometers, and to evaluate the effect of weight loss on this parameter. Research Methods and Procedures: This was a longitudinal, clinical intervention study of a very low‐calorie diet for 4 weeks followed by a low‐calorie diet for 2 months. In 67 severely obese patients, an anthropometric and analytical evaluation [plasmatic lipids, fibrinogen (Fbg), and EA] was performed at baseline and 3 months after diet. The same determinations were performed in 67 normal‐weight volunteers. EA was measured with the Myrenne MA₁, which determines EA at stasis (EA₀) and at a low shear of 3 seconds^?1 (EA₁), and the Sefam aggregometer, which determines aggregation index at 10 seconds^?1 (IA₁₀), aggregation time (Ta), and disaggregation threshold (γD). Insulin resistance (IR) was calculated by homeostasis model assessment. Results: Obese patients showed higher Fbg levels, EA₀, EA₁, IA₁₀, and γD values, and lower Ta values. Differences between obese patients and control group for EA₀, EA₁, Ta, IA₁₀, and γD disappeared after adjusting for BMI or for homeostasis model assessment but were maintained after adjusting for Fbg or low‐density lipoprotein‐cholesterol. Obese patients with IR showed higher EA₀ and EA₁ values. After weight loss, EA₁ showed a significant improvement. Discussion: Obese patients show increased EA. Erythrocyte hyperaggregation does not seem to be related to a high Fbg level or to an abnormal lipid profile but to IR. Hyperagreggation improves after weight loss.