健脾消癌方通过PI3K/Akt信号通路抑制结肠癌血管生成的研究＊

目的 观察结肠癌HCT116细胞健脾消癌方的条件培养液对HUVEC细胞管腔形成的影响，从PI3K/Akt生物轴调控角度探讨其作用机制。方法 培养HCT116细胞，细胞设3组：对照组，健脾消癌方组（加入15%健脾消癌方含药血清）及人参皂苷Rg3组；制备HCT116细胞健脾消癌方条件培养液（分组及制备方法见实验方法），用条件培养液干预HUVEC（脐静脉内皮细胞，Human Umbilical Vein Endothelial Cells），Matrigel基质胶法检测HCT116细胞健脾消癌方条件培养液对HUVEC小管形成的影响。随后采用蛋白免疫印迹法（Western blot）检测各组HCT116细胞磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、p-Akt、VEGF（血管内皮生长因子，Vascular endothelial growth factor）蛋白表达。最后在结肠癌HCT116荷瘤小鼠中验证健脾消癌方对肿瘤生长速度的影响，并经瘤组织VEGF蛋白表达、CD31免疫组化染色检测肿瘤内血管生成情况。结果 模型组HUVEC细胞管腔形成较空白血清组显著增加（P<0.05）；健脾消癌方组及人参皂苷Rg3组较模型组HUVEC细胞管腔形成显著减少（P<0.01）。p-Akt和VEGF蛋白表达水平模型组高于空白血清组（P<0.05），健脾消癌方组及人参皂苷Rg3组显著低于模型组（P<0.01）；PI3K、Akt蛋白表达量组间差异无统计学意义。与对照组比较，模型组荷瘤小鼠肿瘤体积显著性增大，瘤组织内VEGF表达、CD31阳性面积显著性增加，差异有统计学意义（P<0.05）；与模型组比较，健脾消癌方组及人参皂苷Rg3组荷瘤小鼠肿瘤体积显著减小，瘤组织内VEGF表达、CD31阳性面积降低，差异有统计学意义（P<0.05）。结论 健脾消癌方可抑制肿瘤的血管生成和生长，其作用机制可能与PI3K/Akt生物轴调控VEGF表达有关。     

A basal‐enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer‐enriched miRNA is required for prostate tumorigenesis. We identify miR‐205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR‐205 is not required for normal prostate development and homeostasis, genetic deletion of miR‐205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR‐205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR‐205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR‐205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR‐205 in the progression of Pten null‐induced prostate cancer.     

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists

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Mimengosides J and K: two new neuroprotective triterpenoids from the fruits of Buddleja lindleyana

Two new 11-methoxyl substituted triterpenoids, named as mimengosides J (1) and K (2), along with seven known compounds, were isolated from the fruits of Buddleja lindleyana. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the new ones were evaluated for protective effects against damage of SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium ion (MPP⁺) and the results indicated that those may be one of the candidate compositions of Buddleja lindleyana for the treatment of neurodegenerative disease.

     

HPLC-ABTS-DAD-Q-TOF/MS在线检测大黄抗氧化活性成分

目的：建立大黄特征化学成分和抗氧化活性相关联的二维指纹图谱，研究大黄抗氧化活性物质。方法：利用高效液相多检测器联用的抗氧化活性成分在线检测体系，对大黄中化学成分进行检测，共鉴定出大黄中化学成分15种；其中8种具有抗氧化活性；然后采用清除效率为指标对各活性成分的抗氧化活性进行评价。结果：结果发现化合物葡萄糖紫丁香酸、腺嘌呤、没食子酸、儿茶素或表儿茶素、双花母草素、2-O-桂皮酰-没食子酰葡萄糖等具有较强的清除ABTS^·+的活性，而蒽醌类成分对ABTS^·+的清除作用较弱。结论：采用HPLC-ABTS-DAD-Q-TOF/MS对大黄中的抗氧化活性成分进行快速分析鉴定，初步阐明大黄在抗氧化环节起作用的效应物质。     

An Environmental Scan of the National and Provincial Diagnostic Reference Levels in Canada for Common Adult Computed Tomography Scans

Several regulatory bodies have agreed that low-dose radiation used in medical imaging is a weak carcinogen that follows a linear, non-threshold model of cancer risk. While avoiding radiation is the best course of action to mitigate risk, computed tomography (CT) scans are often critical for diagnosis. In addition to the as low as reasonably achievable principle, a more concrete method of dose reduction for common CT imaging exams is the use of a diagnostic reference level (DRL). This paper examines Canada's national DRL values from the recent CT survey and compares it to published provincial DRLs as well as the DRLs in the United Kingdom and the United States of America for the 3 most common CT exams: head, chest, and abdomen/pelvis. Canada compares well on the international scale, but it should consider using more electronic dose monitoring solutions to create a culture of dose optimization.     

丹蛭降糖胶囊通过mTOR/S6K1信号通路对糖尿病肾病大鼠的干预作用研究

目的研究丹蛭降糖胶囊对糖尿病肾病大鼠的肾脏病理改变和足细胞自噬水平的影响,初步探讨其相应的作用机制。方法选取GK大鼠40只,采用醋酸脱氧皮质酮-盐皮下注射联合高脂饲料喂养诱导糖尿病肾病模型。造模成功后随机分为模型组、丹蛭降糖胶囊低剂量组[0.54 g/(kg·d)]、高剂量组[1.08 g/(kg·d)]、缬沙坦组[10 mg/(kg·d)],每组10只。另选取10只同周龄正常Wistar大鼠作为正常组。模型组和正常组给予等容积生理盐水。连续灌胃10周后检测空腹血糖(FBG)、血肌酐(SCr)、尿素氮(BUN)和尿微量蛋白(U-mAlb)。Western Blot检测肾小球p-mTOR、p-S6K1、Beclin-1、LC3和Nephrin蛋白的表达,HE染色和PAS染色后于光镜下观察肾脏病理变化,电镜下观察各组亚细胞形态结构变化。结果与正常组比较,模型组FBG、SCr、BUN、U-mAlb水平升高(P<0.01);与模型组比较,丹蛭降糖胶囊低、高剂量组和缬沙坦组U-mAlb水平降低(P<0.01)。模型组可见肾小球基底膜增厚,系膜基质沉积,足细胞损伤,各用药组均有不同程度改善,丹蛭降糖胶囊高剂量组足细胞内有较多自噬体形成。与正常组比较,模型组p-mTOR、p-S6K1的表达增高,Nephrin、Beclin-1和LC3的表达水平降低(P<0.01);与模型组比较,各用药组p-mTOR、p-S6K1的表达下降,Nephrin、Beclin-1和LC3的表达增高(P<0.01)。丹蛭降糖胶囊高剂量组和缬沙坦组Beclin1、LC3Ⅱ/LC3Ⅰ水平较丹蛭降糖胶囊低剂量组升高(P<0.05)。结论丹蛭降糖胶囊具有减轻糖尿病肾病大鼠U-mAIb、足细胞损伤及相关肾脏病理改变的作用,其机制可能与抑制mTOR/S6K1信号通路进而提高足细胞的自噬活性有关。