Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

Flectin, a protein previously described to be expressed in a left‐dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC‐II) protein class. During looping, both NMHC‐IIA and NMHC‐IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC‐IIB, rather than NMHC‐IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full‐length human NMHC‐IIA and ‐IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC‐IIB antibody does not. Abnormally looping hearts of the Nodal^{Δ 600} homozygous mouse embryos show decreased NMHC‐IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC‐II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping. Developmental Dynamics 237:3577–3590, 2008. © 2008 Wiley‐Liss, Inc.     

How human neutrophils kill and degrade microbes: an integrated view

Summary:  Neutrophils constitute the dominant cell in the circulation that mediates the earliest innate immune human responses to infection. The morbidity and mortality from infection rise dramatically in patients with quantitative or qualitative neutrophil defects, providing clinical confirmation of the important role of normal neutrophils for human health. Neutrophil-dependent anti-microbial activity against ingested microbes represents the collaboration of multiple agents, including those prefabricated during granulocyte development in the bone marrow and those generated de novo following neutrophil activation. Furthermore, neutrophils cooperate with extracellular agents as well as other immune cells to optimally kill and degrade invading microbes. This brief review focuses attention on two examples of the integrated nature of neutrophil-mediated anti-microbial action within the phagosome. The importance and complexity of myeloperoxidase-mediated events illustrate a collaboration of anti-microbial responses that are endogenous to the neutrophil, whereas the synergy between the phagocyte NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and plasma-derived group IIA phospholipase A₂ exemplifies the collective effects of the neutrophil with an exogenous factor to achieve degradation of ingested staphylococci.     

丹参酮ⅡA磺酸钠注射液对冠心病心肌缺血的治疗作用

目的观察丹参酮ⅡA磺酸钠对冠心病心肌缺血的疗效及安全性。方法将77例冠心病患者随机分为A组40例与B组37例。B组常规应用硝酸异山梨酯与阿司匹林。A组在常规治疗基础上加用丹参酮ⅡA碘酸钠注射液。每例于治疗开始前1 d与结束次日,进行血脂、血液流变学与动态心电图(Holter)检测。结果A组查血脂示血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)明显下降(P均<0.01),B组TC、TG、LDL-C治疗前后均无显著性差异(P均>0.05)。A组血液流变学观察示低切变率下全血黏度、高切变率下全血黏度、血浆比黏度、红细胞聚集指数、红细胞比积、血小板聚集率、纤维蛋白原均显著下降(P<0.01或0.05),其改善血液流变学指标的疗效优于B组(P<0.05)。Holter监测示症状性心肌缺血与无症状心肌缺血的发作次数及其持续时间2组均明显减少(P<0.01或0.05),但A组比B组减少更为显著(P均<0.05)。在随访治疗过程中未见丹参酮ⅡA磺酸钠的严重不良反应。结论丹参酮ⅡA磺酸钠有降脂与改善血液流变性作用,是治疗冠心病心肌缺血的一种有效而安全的药物。     

甘西鼠尾草中丹参酮IIA的含量测定

目的测定甘西鼠尾草中丹参酮IIA的含量。方法采用HPLC法,色谱柱:ZORB-AX Eclipe XDB-C18(250×4.6mm,5μm)柱,流动相为:甲醇-水(75:25v/v),检测波长:270nm。结果丹参酮IIA在6.0~100.0μg.m l-1范围内,峰面积与进样浓度线性关系良好,回归方程Y=186.3 245.1C,r=0.9974,平均回收率为98.0%,RSD=1.67%;栽培品甘西鼠尾草中丹参酮IIA含量:1年生0.305%,2年生0.539%,3年生0.776%,野生品0.573%。结论所测样品中丹参酮IIA含量均高于《中国药典》2005年版丹参项下规定要求,且栽培3年生甘西鼠尾草其丹参酮IIA含量高于野生品。     

Tanshinone IIA protects rat primary hepatocytes against carbon tetrachloride toxicity via inhibiting mitochondria permeability transition

Tanshinone IIA (Tan IIA), one of the key components of Salvia milthorrhiza Bunge (Lamiaceae), is used to treat liver disease. The present study was carried out to investigate the possible mechanisms involved in the hepatoprotective effects of Tan IIA on carbon tetrachloride (CCl₄)-induced hepatocyte toxicity. In cultures treated with 1 or 2 μM CCl₄, Tan IIA (10–75 μM) significantly increased hepatocyte survival rates. However, only at a concentration of 75 μM could Tan IIA partially reverse the CCl₄ (3 μM)-induced decrease of survival rate (34?±?3% vs. 18?±?3%, n?=?8, p?<?0.01). In isolated mitochondria energized with succinate, Tan IIA could inhibit the large swelling effect induced by CCl₄ (1 and 2 μM). Base on these results, Tan IIA could protect rat primary cultured hepatocytes from CCl₄-induced toxicity partially by the inhibitory effect on the opening of mitochondrial permeability transition (MPT).     

Ginsenoside Rg1 ameliorates blood–brain barrier disruption and traumatic brain injury via attenuating macrophages derived exosomes miR-21 release

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood–brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1β-induced macrophages (IIM)-Exos-miR-21 can activate NF-κB signaling pathway and induce the expressions of MMP-1, -3 and -9 and downregulate the levels of tight junction proteins (TJPs) deteriorating the BBB. Rg1 reduced miR-21-5p content in IIM-Exos (RIIM-Exos). The interaction of NMIIA–HSP90 controlled the release of Exos-miR-21, this interaction was restricted by Rg1. Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain, enhancing TIMP3 protein expression, MMPs proteolysis, and restricting TJPs degradation thus protected the BBB integrity. Conclusively, Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.     

丹参酮ⅡA磺酸钠对胰腺癌BX-PC-3细胞系增殖与细胞周期调控因子表达的影响

 目的：观察丹参酮ⅡA磺酸钠对胰腺癌细胞系BX-PC-3细胞增殖和细胞周期调控因子cyclin A、cyclin D2蛋白表达的影响。方法：分别用不同剂量的丹参酮ⅡA磺酸钠作用于胰腺癌细胞系BX-PC-3,应用MTT比色法检测培养48 h的细胞存活率, 应用流式细胞术测定培养48 h细胞周期的变化,Western blotting检测周期蛋白cyclin A和cyclin D2 的表达情况。结果：丹参酮ⅡA磺酸钠能明显抑制BX-PC-3细胞增殖,且具有明显的剂量依赖性;流式细胞术显示一定浓度药物作用细胞,可将细胞周期阻滞于G0/G1期;Western blotting检测发现药物能显著下调周期蛋白cyclin A和cyclin D2的表达水平。结论：丹参酮ⅡA磺酸钠能显著抑制人胰腺癌BX-PC-3细胞增殖,下调周期相关因子cyclin A和cyclin D2蛋白表达水平,这可能是丹参酮ⅡA磺酸钠抑制胰腺癌细胞生长增殖的作用机制。     

Tanshinone IIA attenuates interleukin-17A-induced systemic sclerosis patient-derived dermal vascular smooth muscle cell activation via inhibition of the extracellular signal-regulated kinase signaling pathway

OBJECTIVE:Salvia miltiorrhiza has long been used to treat systemic sclerosis. Tanshinone IIA, one of the phytochemicals derived from the roots of Salvia miltiorrhiza, exhibits multiple biological activities. The present study aimed to investigate whether tanshinone IIA has an effect on the interleukin-17A-induced functional activation of systemic sclerosis patient-derived dermal vascular smooth muscle cells.METHODS:Systemic sclerosis patient-derived dermal vascular smooth muscle cells were incubated with various dosages of tanshinone IIA in the presence of interleukin-17A or the serum of systemic sclerosis patients. Cell proliferation was assessed using Cell Counting Kit-8. The expression of collagen 1 and 3 in cells was evaluated by immunofluorescence. Cell migration was measured using a transwell assay. The expression of phospho-extracellular signal-regulated kinase was detected by Western blotting.RESULTS:Our data demonstrate that tanshinone IIA exerts an inhibitory effect on interleukin-17A-induced systemic sclerosis patient-derived dermal vascular smooth muscle cell proliferation, collagen synthesis and migration.CONCLUSION:These findings suggest that tanshinone IIA might serve as a promising therapeutic agent for the treatment of systemic sclerosis.     

丹参酮IIA磺酸钠联合依达拉奉治疗急性脑梗死的疗效研究

目的探讨丹参酮ⅡA磺酸钠联合依达拉奉治疗急性脑梗死的临床疗效及安全性。方法选取100例急性脑梗死患者,随机数字表法分为两组,对照组患者（50例）给予依达拉奉治疗,观察组患者（50例）给予丹参酮ⅡA磺酸钠联合依达拉奉治疗,均治疗14 d。观察并记录两组患者治疗后1个月的疗效,治疗前后ESS评分、SF-36评分及治疗期间不良反应情况。结果治疗后,观察组有效率为90.0%,对照组有效率为72.0%,观察组治疗有效率明显高于对照组（P<0.05）。与治疗前相比,治疗后两组ESS评分均明显增加（P<0.05）,且观察组在治疗3、7、14 d的ESS评分均明显高于对照组（P<0.05）。治疗前两组SF-36各项得分相比,差异没有统计学意义;治疗后,两组SF-36各项得分均明显升高（P<0.05）,且观察组在生理功能、生理职能及精神健康上的评分高于对照组（P<0.05）。治疗期间,两组不良反应率无明显差异。结论丹参酮ⅡA磺酸钠联合依达拉奉对急性脑梗死具有较好的治疗作用,能改善患者神经功能,提高患者生活质量,用药具有安全性,值得临床推广使用。