Cardiovascular & hematological disorders drug targets最新文献

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Cardiovascular & hematological disorders drug targets

Pub Date : 2020-11-26 DOI: 10.2174/1871529x2003201021090604

R. Kones

引用次数: 0

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Cardiovascular & hematological disorders drug targets

Pub Date : 2020-06-14 DOI: 10.2174/1871529x2002200428121739

Chengfeng Bi

引用次数: 0

Protective Effects of TRPV1 Activation Against Cardiac Ischemia/Reperfusion Injury is Blunted by Diet-Induced Obesity TRPV1激活对心脏缺血/再灌注损伤的保护作用被饮食性肥胖削弱

Cardiovascular & hematological disorders drug targets

Pub Date : 2020-06-01 DOI: 10.2174/1871529X19666190912152041

Beihua Zhong, Shuangtao Ma, Donna H. Wang

Background Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study the cardioprotective effects of TRPV1 in obesity. Methods TRPV1 gene knockout (TRPV1-/-) and Wild-Type (WT) mice were Fed a High-Fat Diet (HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo. The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) and reperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 µmol/L) and SP (0.1 µmol/L). Then, Coronary Flow (CF), left ventricular peak positive dP/dt (+dP/dt), Left Ventricular Developed Pressure (LVDP) and Left Ventricular End-Diastolic Pressure (LVEDP) were measured. Results HFD intake remarkably reduced CF, +dP/dt and LVDP and elevated LVEDP in both strains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt and LVDP, and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups. Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05). In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/- mice were improved by CGRP and SP. Conclusion These results suggest that HFD intake impairs cardiac postischemic recovery. HFD-induced impairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/- mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.

瞬时受体电位香草素亚型1 (TRPV1)通道的激活通过释放降钙素基因相关肽(CGRP)和P物质(SP)保护心脏免受缺血/再灌注(I/R)损伤。目前的研究旨在研究TRPV1在肥胖中的心脏保护作用。方法TRPV1基因敲除小鼠(TRPV1-/-)和野生型小鼠(WT)分别饲喂高脂饲料(HFD)和对照饲料(对照组)或20周，取心脏进行离体I/R损伤。分别用辣椒素(10 nmol/L)、CGRP(0.1µmol/L)和SP(0.1µmol/L)孵育后，将心脏置于Langendorff仪上缺血(30 min)和再灌注(40 min)。测量冠状动脉血流(CF)、左室峰值dP/dt阳性(+dP/dt)、左室发育压(LVDP)、左室舒张末期压(LVEDP)。结果HFD显著降低了两种菌株的CF、+dP/dt和LVDP，显著升高了LVEDP (P<0.05)。在对照组小鼠中，辣椒素可降低梗死面积，增加CF、+dP/dt和LVDP，降低LVEDP (P<0.05)，而在其他三组小鼠中则无此作用。CGRP和SP均能显著降低对照组小鼠的梗死面积(P<0.05)。相比之下，CGRP和SP并没有改善HFD喂养的WT和TRPV1-/-小鼠心肌缺血后恢复的所有参数。结论HFD摄入损害了心脏缺血后恢复。CGRP在两种小鼠中均可减轻HFD诱导的恢复损伤，而SP仅在TRPV1-/-小鼠中可减轻CGRP的作用，这表明CGRP和SP的作用在HFD摄入过程中受到不同的调节。

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引用次数: 3

Red Blood Cells are Appropriate Carrier for Coagulation Factor VIII 红细胞是凝血因子VIII的适宜载体

Cardiovascular & hematological disorders drug targets

Pub Date : 2020-05-31 DOI: 10.2174/1871529X19666190918141859

Fatemeh Sayyadipour, N. Amirizadeh, A. Oodi, Masoud Khalili, Fakhredin Saba

Aims Factor VIII (FVIII) replacement therapy remains a primary treatment for hemophilia A, however, the development of FVIII antibodies (inhibitors) and short half-life of the FVIII products are the major complications. Erythrocytes may prevent rapid removal of drugs from plasma. Erythrocytes are biocompatible and non-immunogenic drug delivery. In this study, in vitro activity of FVIII encapsulated by human erythrocytes was investigated. Methods FVIII was loaded into erythrocytes using the hypo-osmotic dialysis technique. FVIII activity assay has been analyzed using Activated Partial Thromboplastin Time (APTT). Presence of FVIII on erythrocytes was detected by western blotting and flowcytometry using specific monoclonal antibody (abcam, U.K) against FVIII. Moreover, the osmotic fragility and hematologic parameters of FVIII-loaded carrier erythrocytes were measured. Results Our results indicated that FVIII could not cross the membrane, where plenty of FVIII was found on the surface of the carrier erythrocyte. Flow cytometery results showed that 11% of the loaded carrier erythrocytes was positive for FVIII protein on their surface. The greatest activation of FVIII in both groups including lysate and non-lysate FVIII-loaded RBCs was observed on the first day, and the coagulant activity of this factor was gradually reduced on days 3 and 5. In 1:50 dilution of both groups, significant differences in FVIII activity were observed in 1:50 dilution of both groups, especially on the 5th day. Conclusion This study aims to introduce erythrocytes as appropriate carriers for FVIII to prolong the dosing intervals in the effective and safe levels for a relatively longer time.

因子VIII (FVIII)替代疗法仍然是a型血友病的主要治疗方法，然而，FVIII抗体(抑制剂)的产生和FVIII产物半衰期短是主要并发症。红细胞可能妨碍药物从血浆中迅速清除。红细胞具有生物相容性和非免疫原性。本研究考察了人红细胞包膜FVIII的体外活性。方法采用低渗透透析技术将FVIII注入红细胞。FVIII活性测定采用活化部分凝血活素时间(APTT)进行分析。使用特异性单克隆抗体(abcam, uk)，通过western blotting和流式细胞术检测FVIII在红细胞中的存在。此外，还测量了fviii载体红细胞的渗透脆性和血液学参数。结果FVIII不能穿过细胞膜，在载体红细胞表面发现大量的FVIII。流式细胞术结果显示，11%的载红细胞表面FVIII蛋白阳性。在两组(包括裂解物和非裂解物装载FVIII的红细胞)中，第一天观察到FVIII的最大激活，并且在第3天和第5天该因子的凝血活性逐渐降低。在1:50稀释时，两组FVIII活性在1:50稀释时差异显著，特别是在第5天。结论本研究旨在引入红细胞作为FVIII的合适载体，延长FVIII在有效和安全水平上的给药间隔时间。

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引用次数: 3

Prognostic Value of Cardiac Biomarkers Assessment in Combination with Myocardial 2D Strain Echocardiography for Early Detection of Anthracycline-Related Cardiac Toxicity 心脏生物标志物评估联合心肌二维应变超声心动图对早期发现蒽环类药物相关心脏毒性的预后价值

Cardiovascular & hematological disorders drug targets

Pub Date : 2020-02-26 DOI: 10.2174/1871529X19666190912150942

M. Mahjoob, Seyed A. Sheikholeslami, Morvarid Dadras, Hamdollah Mansouri, Mahshid Haghi, Mohammadreza Naderian, Leila Sadeghi, M. Tabary, I. Khaheshi

Background: Anthracyclines, a widely used chemotherapy agent with a definite survival improvement, can result in cardiac toxicity presenting with HF (heart failure). Objective: We aim to assess the predictive value of cardiac biomarkers assessment in combination with myocardial two-dimensional strain echocardiography for early detection of cardiac toxicity in patients who underwent Anthracycline-based chemotherapy. Methods: Fifty-two consecutive adult patients scheduled to undergo the first course of Anthracycline-based chemotherapy were subjected to the study. All the patients underwent highly sensitive 2D echocardiographic evaluation before the treatment, 4 and 12 weeks after completion of first-course chemotherapy. Longitudinal and segmental strains were measured. Serum levels of High-sensitive cardiac troponin I (hscTn-I) and N-terminal-pro-BNP (NT-proBNP) were also assessed before the initiation and 3 weeks after completion of first-course chemotherapy. Results: Fifteen patients (28.8%) revealed a decrease in LVEF (Left Ventricular Ejection Fraction) throughout the evaluations, while just 5 patients met the criteria of cardiac toxicity (9.6%). AUC for Global Longitudinal Strain (GLS) ROC curve at 4 weeks of follow-up was calculated to be 0.968. Inferoseptal Systolic Longitudinal Strain (SLS) had the highest AUC value (AUC: 0.934) among different wall SLS. LVESD (Left Ventricular End-Systolic Diameter) at first and second evaluation could predict the risk of cardiac toxicity among LVESD, LVEDD (Left Ventricular End Diastolic Diameter) and LVEDV (Left Ventricular End-Diastolic Volume). Among cardiac biomarkers, hs-cTnI had higher sensitivity, while NT-proBNP had higher specificity for cardiac toxicity. Conclusion: This study has shown that hs-cTnI with good sensitivity can predict cardiac toxicity in Anthracycline-based chemotherapy receiver. The use of strain with speckle echocardiography method has a prognostic value; however, both longitudinal and segmental strain should be assessed. Lateral and inferoseptal SLS (Segmental Longitudinal Strain) are specific markers of cardiac toxicity in the course of anthracycline-related cardiac toxicity.

背景:蒽环类药物是一种广泛使用的化疗药物，具有明确的生存改善，可导致心脏毒性，表现为HF(心力衰竭)。目的:我们旨在评估心脏生物标志物评估联合心肌二维应变超声心动图对蒽环类化疗患者心脏毒性早期检测的预测价值。方法:对52例连续接受蒽环类药物化疗第一疗程的成人患者进行研究。所有患者在治疗前、第一疗程化疗完成后4周和12周均行高灵敏度二维超声心动图评价。测量了纵向应变和分段应变。在开始化疗前和完成第一疗程化疗后3周，还评估了血清中高敏感心肌肌钙蛋白I (hscTn-I)和n端亲bnp (NT-proBNP)水平。结果:15例患者(28.8%)在整个评估过程中出现LVEF(左室射血分数)下降，而只有5例患者(9.6%)符合心脏毒性标准。随访第4周时的全局纵向应变(GLS) ROC曲线AUC为0.968。不同壁间收缩纵向应变(SLS)的AUC值最高，为0.934。LVESD(左室收缩末期内径)、LVEDD(左室舒张末期内径)和LVEDV(左室舒张末期容积)一、二次评价均可预测心脏毒性风险。在心脏生物标志物中，hs-cTnI具有更高的敏感性，而NT-proBNP具有更高的心脏毒性特异性。结论:本研究表明，hs-cTnI具有良好的敏感性，可预测蒽环类药物化疗患者的心脏毒性。采用应变带斑点超声心动图方法对预后有一定价值;然而，纵向应变和分段应变都应进行评估。在蒽环类药物相关的心脏毒性过程中，外侧和隔间节段性纵向应变(SLS)是心脏毒性的特异性标志。

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引用次数: 1

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Cardiovascular & hematological disorders drug targets

Pub Date : 2020-02-26 DOI: 10.2174/1871529x2001200131113131

Donna H. Wang

引用次数: 0

Synergism Effects of Ursolic Acid Supplementation on the Levels of Irisin, C-reactive Protein, IL-6, and TNF-α During High-intensity Resistance Training in Low Activity Men. 补充熊果酸对低活动量男性高强度阻力训练期间鸢尾素、C反应蛋白、IL-6和TNF-α水平的协同效应

Cardiovascular & hematological disorders drug targets

Pub Date : 2020-01-01 DOI: 10.2174/1871529X19666190918144727

Ehsan Asghari, Amir Rashidlamir, Seyyed R A Hosseini, Mahtab Moazzami, Saeed Samarghandian, Tahereh Farkhondeh

Background: Ursolic Acid (UA) is a pentacyclic triterpenoid carboxylic acid which is extracted from plants. UA may enhance the effect of Resistance Training (RT) in human.

Objective: Current research was designed to show the effect of High-Intensity Resistance Training (HIRT) in the presence or absence of UA on the serum levels of irisin, CRP, IL-6 and TNF-α in the low activity men.

Methods: The study included twenty-two healthy male HIRT with placebo, supplementation, and HIRT in the presence of UA supplementation. The two groups received eight-week intervention including 2 sets of 8 exercises, with 8~10 repetitions at 70~75% of 1 repetition maximum and a 2 min rest interval between sets, performed 3 times/week. Placebo or UA orally was evaluated as 1 capsule 3 times/day during 8 weeks. The subsequent factors were measured post- and preintervention: C-Reactive Protein (CRP), Irisin, Tumor Necrotic Factor (TNF-α) and Interleukin-6 (IL-6).

Results: UA supplementation significantly increased the plasma levels of irisin in the HIRT+UA group versus the HIRT+P group (p<0.05). UA treatment also dramatically decreased the plasma levels of CRP, IL-6, and TNF-α in the HIRT+UA group versus the HIRT+P group (p<0.05).

Conclusion: The current data showed that UA-induced an increase in serum irisin and reduction of CRP, IL-6, and TNF-α may have beneficial effects as a chemical for increasing of the effects of HIRT in low activity men.

背景：熊果酸（UA）是从植物中提取的五环三萜类羧酸。UA 可增强人体阻力训练（RT）的效果：目前的研究旨在显示在有或没有 UA 的情况下进行高强度阻力训练（HIRT）对低活动量男性血清中鸢尾素、CRP、IL-6 和 TNF-α 水平的影响：研究包括 22 名健康男性 HIRT，分别服用安慰剂、补充剂，以及在补充 UA 的情况下服用 HIRT。两组均接受为期八周的干预，包括 2 组共 8 个练习，以最大重复次数的 70% 至 75% 重复 8 至 10 次，组间休息 2 分钟，每周进行 3 次。口服安慰剂或 UA，每次 1 粒，每天 3 次，共 8 周。对干预后和干预前的后续因素进行了测量：结果发现，补充尿酸能显著提高血浆中尿酸水平：结果：补充 UA 后，HIRT+UA 组与 HIRT+P 组相比，血浆鸢尾素水平明显升高（p）：目前的数据表明，UA 引起的血清鸢尾素的增加和 CRP、IL-6 和 TNF-α 的降低可能会对低活动量男性产生有益的影响，可作为增加 HIRT 效果的化学物质。

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引用次数: 6

Effect of Terebinthus atlanticus on Glucose Metabolism in Diabetic Rats. 大西洋风信子对糖尿病大鼠葡萄糖代谢的影响

Cardiovascular & hematological disorders drug targets

Pub Date : 2020-01-01 DOI: 10.2174/1871529X19666190902124018

Fadwa El-Ouady, Lhoussaine Hajji, Mohamed Eddouks

Background: Terebinthus atlanticus (Anacardiaceae) is an important source of essential oil and phenolic compounds justifying its use in traditional medicine.

Objective: The present work aimed to evaluate the antidiabetic and the antioxidant activities of the aqueous extract of the leaves of Terebinthus atlanticus (T. atlanticus).

Methods: The current study evaluated the effect of a single and repeated (15 days of treatment) oral administration of the aqueous extract of the leaves of T. atlanticus (PALAE) on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rats. Furthermore, the effect of PALAE on glucose tolerance and histopathological examination of the liver was carried out.

Results: A single oral administration of PALAE reduced blood glucose levels in normal (p<0.05), and STZ diabetic rats (p<0.0001), 6 and 4 hours after administration, respectively. Furthermore, this extract had an optimal effect (p<0.0001) in both normal and STZ diabetic rats at the 15th and 7th day of treatment. This extract was also shown to prevent significantly the increase on blood glucose levels 120 min after glucose administration, in both normal (p<0.05), and diabetic (p<0.01) treated rats when compared to the control group. In addition, the histopathological analysis highlighted the positive effect of T. atlanticus on pancreas and liver.

Conclusion: The study demonstrates the antihyperglycemic effect of the aqueous T. atlanticus extracts in diabetic rats which should be mediated through the amelioration of the oxidative stress as well as an improvement in liver histology.

背景：大西洋风信子（Anacardiaceae）是精油和酚类化合物的重要来源，因此被用于传统医学：本研究旨在评估大西洋风信子（T. atlanticus）叶水提取物的抗糖尿病和抗氧化活性：本研究评估了单次和重复（15 天治疗）口服大西洋刺芹叶水提取物（PALAE）对正常大鼠和链脲佐菌素（STZ）诱导的糖尿病大鼠血糖水平的影响。此外，还研究了 PALAE 对葡萄糖耐量和肝脏组织病理学检查的影响：结果：单次口服 PALAE 可降低正常大鼠（p）的血糖水平：该研究证明了大西洋蟾蜍水提取物对糖尿病大鼠的降血糖作用，这种作用应通过改善氧化应激和肝脏组织学来实现。

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引用次数: 0

Ethyl acetate and aqueous fractions of Ziziphus jujuba prevent acute hypertension induced by angiotensin II in rats. 乙酸乙酯和酸枣水馏分对血管紧张素ⅱ诱导大鼠急性高血压有预防作用。

Cardiovascular & hematological disorders drug targets

Pub Date : 2019-11-19 DOI: 10.2174/1871529X19666191119141400

Y. Kamkar-Del, R. Mohebbati, M. Hoseini, A. Khajavirad, M. Shafei, H. Rakhshande

BACKGROUNDAntihypertensive effect of Ziziphus jujube (ZJ) has been reported previously.OBJECTIVEThe present study investigates the effect of two ethyl acetate (polar and semi-polar compound) and aqueous fractions (polar compound) of ZJ on cardiovascular parameters in acute hypertension induced by angiotensin II(AngII).METHODSRats randomly were divided into as following groups (n=7 in each group): Control, AngII (50 ng/kg), Losartan (Los, 30 mg/kg) + AngII, ethyl acetate fraction (EA150 and EA300 mg/kg) + AngII and aqueous fraction (A150 and A300 mg/kg) + AngII. Treated rats received Los and ZJ fractions for four weeks orally and in experiment day (28th) received AngII intravenously. In all groups' systolic blood pressure (SBP), heart rate (HR) and mean arterial pressure (MAP) were recorded throughout the experiment after cannulation of femoral artery via power lab system.RESULTSIn AngII group SBP and MAP significantly increased (P<0.001) and HR decreased compared to the control. The SBP and MAP in both doses (150 and 300 mg/kg) of two fractions significantly were reduced in comparison with the AngII group (P<0.05, P<0.001, respectively). Bradycardia induced by AngII also decreased so was not significant than control. Comparison the effects of two fractions revealed that both fractions reduced cardiovascular responses induced by AngII but ethyl acetate is more effective than aqueous fraction.CONCLUSIONThis study indicates that the both fractions of the ZJ extract have beneficial effect on AngII hypertensive in rat. Because the most compounds of two fractions are polar, we suggested that antihypertensive effects of ZJ is mediated by polar compounds.

背景:酸枣(Ziziphus jube, ZJ)的降压作用已有报道。目的探讨ZJ的两乙酸乙酯(极性和半极性化合物)和水溶液(极性化合物)对血管紧张素II(AngII)诱导的急性高血压患者心血管参数的影响。方法将大鼠随机分为对照组、AngII (50 ng/kg)组、氯沙坦(Los, 30 mg/kg) + AngII、乙酸乙酯部分(EA150和EA300 mg/kg) + AngII和水溶液部分(A150和A300 mg/kg) + AngII组，每组7只。大鼠连续4周口服Los和ZJ组份，实验第28天静脉注射AngII。实验过程中，通过动力实验室系统记录各组大鼠股动脉插管后的收缩压(SBP)、心率(HR)和平均动脉压(MAP)。结果与对照组相比，AngII组患者收缩压、MAP显著升高(P<0.001)， HR显著降低。与AngII组相比，150和300 mg/kg两种剂量下的收缩压和MAP均显著降低(P<0.05, P<0.001)。AngII诱导的心动过缓也有所减少，但与对照组相比无显著性差异。结果表明，两种组分均能降低AngII诱导的心血管反应，但乙酸乙酯组分的效果优于水组分。结论ZJ提取物两组分均对大鼠ii型高血压有一定的治疗作用。由于两组分中大多数化合物都是极性的，因此我们认为ZJ的降压作用可能是由极性化合物介导的。

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引用次数: 6

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Cardiovascular & hematological disorders drug targets

Pub Date : 2019-10-21 DOI: 10.2174/1871529x1903191021173535

E. Arellano-Rodrigo

引用次数: 0

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