乙酰肝素酶(heparanase,HPA)是目前发现的哺乳动物细胞中唯一能切割硫酸乙酰肝素蛋白多糖(heparansulfateproteoglycans,HSPGs)侧链的葡萄糖醛酸内切酶,参与细胞外基质的降解和重塑,是目前抗肿瘤转移的理想靶点。HPA也表现出非酶活性,如HPA的黏附作用促进肿瘤细胞获得转移能力、HPA介导核内组蛋白促进肿瘤侵袭转移等。该文就现阶段HPA在肿瘤细胞转移过程的非酶活性研究进展作一综述。
目的通过动态检测急性胰腺炎(AP)患者外周血清C反应蛋白(CRP)、脂肪酶(LPS)、白细胞介素(IL)1β和细胞间黏附分子(ICAM)1的水平及变化,评价多种指标联合检测在AP临床诊断中的价值。方法收集2010年1月-2012年12月在中国医科大学附属第四医院进行治疗的AP患者86例,其中重症急性胰腺炎(SAP)患者39例,轻症急性胰腺炎(MAP)患者47例。于入院第1、3、5、7天分别采集患者血清,另选取12例同期健康体检者作为对照。采用ELISA法检测血清中CRP、IL-1β和ICAM-1水平,干片速率法测定血清LPS的浓度。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果

LY2157299细胞系 MAP组患者入院第1天的CRP、IL-1β和LPS水平明显高于对照组,差异均有统计学意义(t值分别为-74.126、-60.135、-364.153,P值均<0.001);SAP组患者入院第1天的CRP、ICAM-1、IL-1β、LPS水平均明显高于对照组,差异亦有统计学意义(t值分别为-121.355、-25.728、-89.422、-415.840,P值均<0.001);各检测指标浓度的峰值出现在入院第1天或第3天,且随着治疗时间的延长,浓度呈进行性下降;与MAP患者相比,SAP患者血清中CRP、LPS、IL-1β和ICAM-1水平均较高,差异均有统计学意义(P值均<0.05)。结论联合检测患者血清CRP、LPS、IL-1β和ICAM-1水平对于AP严重程度的早期判断具有一定的临床参考价值。
To date,more GSK2656157 than 27,000 drugs are available to treat disease worldwide.The discovery of a new drug requires an average of 13 years of research and an investment of US$1.8 billion to bring a single drug

from the bench to a patient’s bedside(Figure1).Another approach,termed”new uses for old drugs”,”drug
NFAT5 plays a critical role in maintaining the renal functions. Its dis-regulation in the kidney leads to or is associated with certain renal diseases or disorders, most notably the urinary concentration defect. Hypertonicity, which the kidney medulla is normally exposed to, activates NFAT5 through phosphorylation of a signaling molecule or NFAT5 itself. Hypotonicity inhibits NFAT5 through a similar mechanism. More than a dozen of protein and lipid kinases have

been identified to contribute to tonicity-dependent regulation of NFAT5. Hypertonicity activates NFAT5 by increasing its nuclear localization and transactivating activity in the early phase and protein abundance in the late phase. The known mechanism TPCA-1体内 for inhibition of NFAT5 by hypotonicity is a decrease of nuclear NFAT5. The present article reviews the effect of each kinase on NFAT5 nuclear localization, transactivation and protein abundance, and the relationship among these kinases, if known. Cyclosporine A and tacrolimus suppress immune reactions by inhibiting the phosphatase calcineurin-dependent activation of NFAT1. It is hoped that this review would stimulate the interest to seek explanations from the NFAT5 regulatory pathways for certain clinical presentations and to explore novel therapeutic approaches based on the pathways. On the basic science front, this review raises two interesting questions. The first one is how these kinases can specifically signal to NFAT5 in the context of hypertonicity or hypotonicity, because they also regulate other cellular activities and even opposite activities in some cases.