Store–Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression

Accumulation of extracellular matrix derived from glomerular mesangial cells is an early feature of diabetic nephropathy. Ca²⁺ signals mediated by store–operated Ca²⁺ channels regulate protein production in a variety of cell types. The aim of this study was to determine the effect of store–operated Ca²⁺ channels in mesangial cells on extracellular matrix protein expression. In cultured human mesangial cells, activation of store–operated Ca²⁺ channels by thapsigargin significantly decreased fibronectin protein expression and collagen IV mRNA expression in a dose-dependent manner. Conversely, inhibition of the channels by 2-aminoethyl diphenylborinate significantly increased the expression of fibronectin and collagen IV. Similarly, overexpression of stromal interacting molecule 1 reduced, but knockdown of calcium release–activated calcium channel protein 1 (Orai1) increased fibronectin protein expression. Furthermore, 2-aminoethyl diphenylborinate significantly augmented angiotensin II–induced fibronectin protein expression, whereas thapsigargin abrogated high glucose– and TGF-β1–stimulated matrix protein expression. In vivo knockdown of Orai1 in mesangial cells of mice using a targeted nanoparticle siRNA delivery system resulted in increased expression of glomerular fibronectin and collagen IV, and mice showed significant mesangial expansion compared with controls. Similarly, in vivo knockdown of stromal interacting molecule 1 in mesangial cells by recombinant adeno–associated virus–encoded shRNA markedly increased collagen IV protein expression in renal cortex and caused mesangial expansion in rats. These results suggest that store–operated Ca²⁺ channels in mesangial cells negatively regulate extracellular matrix protein expression in the kidney, which may serve as an endogenous renoprotective mechanism in diabetes.     

中国沉香科技创新与产业发展的现状及思考

沉香为我国名贵中药和香料。中国沉香产业既是传统产业也是可培育为千亿元的新兴产业,市场潜力巨大,但目前仍处于初级发展阶段。本文从科学技术创新的角度阐述了中国沉香产业的发展现状和取得的成绩,分析了中国沉香科技和产业发展存在的问题,在此基础上提出几点发展思路,为中国沉香产业发展提供参考。     

世界各国沉香资源与保护

沉香是亚洲各国传统名贵药材及天然香料,瑞香科（Thymelaeaeeae）中的沉香属（Aquilaria）是其最主要的结香树种。随着沉香市场的发展及沉香属自然生存生境的破坏,属内大多数物种现已濒临灭绝。为了更好地保护以及开发利用该属资源,本文对世界上各个国家沉香属植物的野生分布及资源现状、人工种植现状、采集贸易和保护现状等方面进行了简要概述,并从可持续发展的角度出发,提出了保护与开发利用沉香资源的一些建议。     

Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening

Natural killer (NK) cells play important roles in controlling virus-infected and malignant cells. The identification of new molecules that can activate NK cells may effectively improve the antiviral and antitumour activities of these cells. In this study, by using a commercially available metabolism-related compound library, we initially screened the capacity of compounds to activate NK cells by determining the ratio of interferon-gamma (IFN-γ)⁺ NK cells by flow cytometry after the incubation of peripheral blood mononuclear cells (PBMCs) with IL-12 or IL-15 for 18 h. Our data showed that eight compounds (nafamostat mesylate (NM), loganin, fluvastatin sodium, atorvastatin calcium, lovastatin, simvastatin, rosuvastatin calcium, and pitavastatin calcium) and three compounds (NM, elesclomol, and simvastatin) increased the proportions of NK cells and CD3⁺ T cells that expressed IFN-γ among PBMCs cultured with IL-12 and IL-15, respectively. When incubated with enriched NK cells (purity?≥?80.0%), only NM enhanced NK cell IFN-γ production in the presence of IL-12 or IL-15. When incubated with purified NK cells (purity?≥?99.0%), NM promoted NK cell IFN-γ secretion in the presence or absence of IL-18. However, NM showed no effect on NK cell cytotoxicity. Collectively, our study identifies NM as a selective stimulator of IFN-γ production by NK cells, providing a new strategy for the prevention and treatment of infection or cancer in select populations.

     

尿激酶静脉溶栓治疗急性心肌梗死的临床观察

目的观察评价尿激酶静脉溶栓治疗急性心肌梗死临床疗效,分析用药时机、剂量对患者预后的影响。方法我院2009年4月至2013年8月应用尿激酶静脉溶栓治疗急性心肌梗死35例,行回顾性分析,统计对比不同溶栓时间患者再通率、死亡率、并发率、不良反应发生率。结果 <3 h溶栓者12例、3~6 h溶栓者15例、>6 h溶栓者8例;<3 h溶栓者与≥3 h溶栓者年龄、性别、合并症、梗死部位、吸烟、饮酒、高同型半胱胺酸血症、HCY水平差异无统计学意义(P>0.05);不同时间应用尿激酶溶栓再通率差异无统计学意义(P>0.05);溶栓再通20例,平均溶栓时间(1.9±1.5)h,低于溶栓失败15例(4.3±1.0)h,差异具有统计学意义(P<0.05);血管再通再灌注心率失常发生率与发生类型差异无统计学意义(P>0.05);死亡2例,死亡率5.71%,<3 h溶栓者、病发≥6 h溶栓者死亡率、肺水肿发生率、牙龈出血率差异无统计学意义(P>0.05);<3 h溶栓者、≥6 h溶栓者心源性休克发生率差异具有统计学意义(P<0.05)。结论<3h,应积极行尿激酶溶栓,有助于降低并发、死亡风险,发病3~6 h可以溶栓,大于6 h不应溶栓,可增加并发风险,收益小,风险高。     

突发公共卫生事件形势下医学文献资源保障与服务

以上海交通大学医学院图书馆为例,介绍文献资源服务模式与内容,阐述新型冠状病毒肺炎疫情期间数字资源保障服务举措并提出相关建议,包括多平台结合保障远程资源获取,鼓励并规范出版商资源开放与公益服务,创新发展在线教育健全服务推广。