Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells

Chronic infection with Helicobacter pylori cagA‐positive strains is causally associated with the development of gastric diseases, most notably gastric cancer. The cagA‐encoded CagA protein, which is injected into gastric epithelial cells by bacterial type IV secretion, undergoes tyrosine phosphorylation at the Glu‐Pro‐Ile‐Tyr‐Ala (EPIYA) segments (EPIYA‐A, EPIYA‐B, EPIYA‐C, and EPIYA‐D), which are present in various numbers and combinations in its C‐terminal polymorphic region, thereby enabling CagA to promiscuously interact with SH2 domain‐containing host cell proteins, including the prooncogenic SH2 domain‐containing protein tyrosine phosphatase 2 (SHP2). Perturbation of host protein functions by aberrant complex formation with CagA has been considered to contribute to the development of gastric cancer. Here we show that SHIP2, an SH2 domain‐containing phosphatidylinositol 5′‐phosphatase, is a hitherto undiscovered CagA‐binding host protein. Similar to SHP2, SHIP2 binds to the Western CagA‐specific EPIYA‐C segment or East Asian CagA‐specific EPIYA‐D segment through the SH2 domain in a tyrosine phosphorylation‐dependent manner. In contrast to the case of SHP2, however, SHIP2 binds more strongly to EPIYA‐C than to EPIYA‐D. Interaction with CagA tethers SHIP2 to the plasma membrane, where it mediates production of phosphatidylinositol 3,4‐diphosphate [PI(3,4)P₂]. The CagA‐SHIP2 interaction also potentiates the morphogenetic activity of CagA, which is caused by CagA‐deregulated SHP2. This study indicates that initially delivered CagA interacts with SHIP2 and thereby strengthens H. pylori‐host cell attachment by altering membrane phosphatidylinositol compositions, which potentiates subsequent delivery of CagA that binds to and thereby deregulates the prooncogenic phosphatase SHP2.     

表面等离子共振技术在中医药研究中应用进展

利用表面等离子共振现象制备的生物传感技术具有无标记、灵敏度高、通量大、特异性强，样品耗损少等优点，在生命科学等众多学科中得到了广泛的关注和应用。近年来该技术也被运用在不少中医药研究的重要领域。本文简要介绍了表面等离子共振原理，总结并评述了在中医药新靶标发现、优效小分子寻找等方向的研究进展和前景。     

温针灸阳陵泉穴治疗膝关节骨性关节炎临床疗效观察

目的:观察温针灸阳陵泉穴治疗膝关节骨性关节炎的临床疗效。方法:将2015年1月至2019年1月本院收治的膝关节骨性关节炎患者120例,根据随机数字表法分为对照组和观察组,每组60例。对照组给予等速肌力训练治疗,观察组在对照组的基础上加用温针灸阳陵泉穴治疗。观察两组患者膝关节屈曲度、伸直度,白细胞介素(interleukin,IL)-6及IL-18水平,VAS评分及膝关节症状和功能评分。结果:观察组治疗后屈曲度及伸直度均高于对照组,差异有统计学意义(P<0.05);观察组治疗后IL-6及IL-18水平均低于对照组,差异有统计学意义(P<0.05);观察组治疗后VAS评分低于对照组,差异有统计学意义(P<0.05);观察组治疗后症状和功能评分高于对照组,差异有统计学意义(P<0.05);观察组有效率95.0%,对照组有效率83.3%,观察组有效率高于对照组,差异有统计学意义(P<0.05)。结论:温针灸阳陵泉穴治疗膝关节骨性关节炎,可有效改善患者膝关节活动度,降低炎症因子,减轻疼痛,提高临床疗效。     

早期电针干预对SAMP8小鼠学习记忆能力和海马磷酸化Tau蛋白水平的影响

目的:探讨早期电针"百会""大椎""肾俞"穴对快速老化小鼠(SAMP8小鼠)学习记忆能力和海马磷酸化Tau蛋白表达的影响,为临床电针治疗阿尔茨海默病(AD)时间点的选择提供参考。方法:将36只3月龄SAMP8小鼠随机分为模型组、3月龄电针组、9月龄电针组,每组12只;以12只同龄正常老化SAMR1小鼠作为空白对照组。3月龄电针组及9月龄电针组分别于小鼠3月龄及9月龄时予电针"百会""大椎""肾俞"穴治疗(连续波,2 Hz,1.5~2 mA),20 min/次,每日1次,8 d为一疗程,疗程间隔2 d,共治疗3个疗程。每组小鼠在水迷宫检测学习记忆能力结束后统一于10月龄取材;免疫组织化学法、免疫蛋白印迹法(Western blot)检测小鼠海马磷酸化Tau蛋白的表达,实时荧光定量PCR法检测小鼠海马Tau mRNA表达。结果:与空白对照组比较,模型组小鼠逃避潜伏期明显延长(P<0.01),原平台象限停留时间较短,跨越平台次数减少(P<0.01),海马磷酸化Tau蛋白及Tau mRNA表达较高(P<0.01);与模型组比较,3月龄电针组及9月龄电针组小鼠逃避潜伏期缩短(P<0.05),原平台象限停留时间延长,跨越平台次数增多(P<0.05),小鼠海马磷酸化Tau蛋白及Tau mRNA表达降低(P<0.05);与9月龄电针组比较,3月龄电针组小鼠逃避潜伏期缩短(P<0.05),原平台象限停留时间延长,跨越平台次数增多(P<0.05),海马磷酸化Tau蛋白及Tau mRNA表达降低(P<0.01)。结论:早期电针干预能更有效地改善SAMP8小鼠学习记忆能力并降低其海马磷酸化Tau蛋白水平。