Altered platelet calsequestrin abundance,Na/Ca exchange and Ca signaling responses with the progression of diabetes mellitus

Introduction

Downregulation of calsequestrin (CSQ), a major Ca^2 + storage protein, may contribute significantly to the hyperactivity of internal Ca^2 + ([Ca^2 +]_i) in diabetic platelets. Here, we investigated changes in CSQ-1 abundance, Ca^2 + signaling and aggregation responses to stimulation with the progression of diabetes, especially the mechanism(s) underlying the exaggerated Ca^2 + influx in diabetic platelets.

Materials and methods

Type 1 diabetes was induced by streptozotocin in rats. Platelet [Ca^2 +]_i and aggregation responses upon ADP stimulation were assessed by fluorescence spectrophotometry and aggregometry, respectively. CSQ-1 expression was evaluated using western blotting.

Results

During the 12-week course of diabetes, the abundance of CSQ-1, basal [Ca^2 +]_i and ADP-induced Ca^2 + release were progressively altered in diabetic platelets, while the elevated Ca^2 + influx and platelet aggregation were not correlated with diabetes development. 2-Aminoethoxydiphenyl borate, the store-operated Ca^2 + channel blocker, almost completely abolished ADP-induced Ca^2 + influx in normal and diabetic platelets, whereas nifedipine, an inhibitor of the nicotinic acid adenine dinucleotide phosphate receptor, showed no effect. Additionally, inhibition of Na⁺/Ca^2 + exchange induced much slower Ca^2 + extrusion and more Ca^2 + influx in normal platelets than in diabetic platelets. Furthermore, under the condition of Ca^2 +-ATPase inhibition, ionomycin caused greater Ca^2 + mobilization and Ca^2 + influx in diabetic platelets than in normal platelets.

Conclusions

These data demonstrate that platelet hyperactivity in diabetes is caused by several integrated factors. Besides the downregulation of CSQ-1 that mainly disrupts basal Ca^2 + homeostasis, insufficient Na⁺/Ca^2 + exchange also contributes, at least in part, to the hyperactive Ca^2 + response to stimulation in diabetic platelets.     

Bubble-propelled micromotors based on hierarchical MnO2 wrapped carbon nanotube aggregates for dynamic removal of pollutants

Water pollution is currently an urgent public health and environmental issue. Bubble-propelled micromotors might offer an effective approach for dealing with environmental contamination. Herein, we present the synthesis of multi-walled carbon nanotube (MWCNT)/manganese dioxide (MnO₂) micromotors based on MWCNT aggregates as microscale templates by a simple one-step hydrothermal procedure. The morphology, composition, and structure of the obtained MWCNT/MnO₂ micromotors were characterized in detail. The MnO₂ nanoflakes formed a catalytic layer on the MWCNT backbone, which promoted effective bubble evolution and propulsion at remarkable speeds of 359.31 μm s⁻¹. The bubble velocity could be modulated based on the loading of MnO₂ nanoflakes. The rapid movement of these MWCNT/MnO₂ catalytic micromotors resulted in a highly efficient moving adsorption platform, which considerably enhanced the effectiveness of water purification. Dynamic adsorption of organic dyes by the micromotors increased the degradation rate to approximately 4.8 times as high as that of their corresponding static counterparts. The adsorption isotherms and adsorption kinetics were also explored. The adsorption mechanism was well fitted by the Langmuir model, following pseudo-second-order kinetics. Thus, chemisorption of Congo red at the heterogeneous MnO₂ wrapped microimotor surface was the rate determining step. The high propulsion speed and remarkable decontamination efficiency of the MWCNT/MnO₂ micromotors indicate potential for environmental contamination applications.

Water pollution is currently an urgent public health and environmental issue.     

高频超声对膝关节半月板急慢性损伤的诊断价值分析

目的分析探讨高频超声对膝关节半月板急慢性损伤的诊断价值。方法选取2017年1月至2018年2月牡丹江医学院第二附属医院收治的50例膝关节半月板急慢性损伤患者(设为研究组)及50例健康体检者(设为对照组)作为研究对象,应用高频超声检测其膝关节滑膜厚度、髌上囊积液深度及滑膜血流状况,并予以对比。结果研究组患者膝关节半月板在基线外侧较为突出且可见点状或条状强回声区,内侧副韧带变形,部分患者伴有不同程度的水肿,滑膜厚度为(6.25±2.20) mm,髌上囊积液深度为(7.35±1.45) mm,滑膜血流为0级者23例、Ⅰ级者12例、Ⅱ级者12例、Ⅲ级者3例;对照组研究对象膝关节半月板回声强度中等且均匀,边缘清晰,滑膜厚度为(1. 10±0.46) mm,髌上囊积液深度为(2. 12±0.43) mm,滑膜血流为0级者38例、Ⅰ级者12例。两组研究对象膝关节滑膜厚度、髌上囊积液深度及滑膜血流状况对比,P均0.01,差异具有统计学意义。结论高频超声对膝关节滑膜厚度、髌上囊积液及滑膜血流均较敏感,在膝关节半月板急慢性损伤的诊断中特异性较高,且操作简便,可作为膝关节半月板急慢性损伤的首选诊断方法予以推广、普及。     

血管化肋软骨结合纤毛化内皮内壁的人工气管重建

目的：探讨血管化肋软骨结合纤毛化内皮内壁合成人工气管重建气管长段及特殊缺损的可行性,建立与天然气管的生理结构、功能更接近的人工气管模型。方法以8例新西兰白兔为动物实验模型,I期颈部双层带血供筋膜包埋培养自体肋软骨和鼻中隔黏膜,II期人工气管原位移植,术后定期评估生理、呼吸及病理学等指标。结果8例实验兔II期术后平均存活时间21.9 d,死亡原因为呼吸困难。人工气管组织解剖可见瘢痕增生,无塌陷,有弹性和硬度。组织病理可见肋软骨和气管环软骨在组织学上有较高相似度;肋软骨在带血供筋膜包裹培养下均未被吸收,仍可见肋软骨组织;鼻中隔黏膜在体内加压及带血供筋膜营养下继续分化,HE染色切片下可见人工气管内壁覆有上皮样组织。结论肋软骨可作为制备人工气管塑形材料;包裹肋软骨的带血供筋膜可提供充足的血供,弥补了游离培养肋软骨致其吸收的缺陷;鼻中隔黏膜在体内加压及带血供筋膜的营养下,有望模拟气管纤毛上皮,从而发挥其与气管内壁相似的生物学特性。     

天然产物防治急性肺损伤的作用机制研究进展

急性肺损伤(acute lung injury,ALI)是临床上常见的危重病症,发病率和致死率逐年增高,其本质为炎症反应失衡,引发弥漫性肺泡及肺血管内皮细胞损伤、肺组织水肿及肺不张等病理特征。其调控途径涉及NF-κB、MAPK等信号通路和TLRs、PPARγ、腺苷A2A等主要相关受体。天然产物在防治ALI方面日益受到关注,其作用机制研究也不断深入。本文综述近3年来天然产物对ALI病理特征的改善作用及其所涉及的信号通路和相关受体,以期为研制防治ALI的创新药物提供一定线索和依据。     

基于临床参考及基因因素建立华法林稳定维持剂量预测模型

目的 探讨华法林应用的临床参考因素及基因因素与华法林稳定维持剂量的相关性,并尝试构建适用于非瓣膜病心房纤颤（non-valvular-disease atrial fibrillation,NVAF）患者华法林稳定维持剂量的预测模型。方法 按照纳入标准共纳入126例患者,应用测序反应通用试剂盒及荧光检测仪检测细胞色素P450 2C9和维生素K环氧化物还原酶基因多态性,同时记录华法林应用的临床参考因素：年龄、体质量、房颤栓塞风险评分系统（CHA₂DS₂-VASc）评分、房颤出血风险评分系统（HAS-BLED）评分、谷丙转氨酶（glutamic-pyruvic transaminase,ALT）、肾小球滤过率（glomerular filtration rate,GFR）、左心室射血分数（left ventricular ejection fraction,LVEF）、二尖瓣环水平左室侧壁组织多普勒S波;采用相关性分析探讨临床参考因素及基因多态性与华法林稳定维持剂量的相关性,并通过多元线性回归建立了华法林稳定维持剂量预测模型。结果 体质量、ALT水平、二尖瓣环水平左室侧壁组织多普勒S波与华法林稳定维持剂量成正相关,年龄、CHA₂DS₂-VASc评分、HAS-BLED评分则成负相关,而LVEF、GFR未显示明显的相关性。建立的预测模型对已有样本验证准确率达55.6%。结论 该模型可用于预测NVAF患者华法林稳定维持剂量。