microRNA-489 Plays an Anti-Metastatic Role in Human Hepatocellular Carcinoma by Targeting Matrix Metalloproteinase-7

Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of hepatocellular carcinoma (HCC). miR-489 was found to play either oncogenic or tumor suppressive roles in human cancers. Recent study reported that the levels of miR-489 in late recurrent HCC patients were evidently higher than that in early recurrent cases, suggesting that miR-489 may function as a tumor suppressive miRNA in HCC. Yet, the clinical value and biological function of miR-489 remain rarely known in HCC. Here, we presented that miR-489 level in HCC tissues was notably reduced compared to matched non-cancerous specimens. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of HCC patients. Accordingly, the levels of miR-489 were obviously down-regulated in HCC cells. Ectopic expression of miR-489 in HCCLM3 and MHCC97H cells prominently inhibits the migration and invasion of tumor cells and reduced lung metastases in vivo, while miR-489 knockdown increased these behaviors of HepG2 and MHCC97L cells. Mechanically, miR-489 negatively regulated matrix metalloproteinase-7 (MMP7) abundance in HCC cells. Herein, MMP7 was found to be a downstream molecule of miR-489 in HCC. An inversely correlation between miR-489 and MMP7 was confirmed in HCC specimens. MMP7 knockdown prohibited cell migration and invasion while MMP7 overexpression showed opposite effects on HCC cells. Furthermore, restoration of MMP7 expression could abrogate the anti-metastatic effects of miR-489 on HCCLM3 cells with enhanced cell migration and invasion. Altogether, miR-489 potentially acts as a prognostic predictor and a drug-target for HCC patients.     

Mechanisms of killing of measles virus-infected cells by human lymphocytes: interferon associated and unassociated cell-mediated cytotoxicity

The recent interest in natural killer (NK) cells in immunosurveillance and the ability of infection with certain organisms to modulate NK activity led us to examine the influence of Toxoplasma gondii infection on mouse NK cells. Infection of BALB/c mice with 5 × 10³ virulent Toxoplasma intraperitoneally (ip) resulted in significantly enhanced NK activity in peritoneal exudate cells (PC) and in spleen cells (SC). Intravenous (iv) and subcutaneous (sc) challenge of BALB/c mice with Toxoplasma also resulted in enhanced natural killer (NK) activity in PC and SC. In BALB/c mice, as well as in other strains (A/J, C57BL/6, C3H/HeJ, CeH/HeN, [A/J × C3H]F₁), peak augmentation of PC and SC NK activity was observed 3 days following ip Toxoplasma challenge. Administration of silica to mice abolished Toxoplasma-induced NK cytotoxicity. BALB/c mice chronically infected with Toxoplasma had significantly higher endogenous NK activity than did controls in PC but not in SC. Chronically infected BALB/c mice boosted with virulent Toxoplasma ip exhibited significantly enhanced NK activity in PC but not in SC. Thus, acute and chronic infection with Toxoplasma modulates NK activity in addition to macrophage activation and thereby provides a system that should facilitate study of the relative contribution of NK cells and activated macrophages in resistance to tumor growth and spread.     

青蒿素的发现与研究进展

1967年北京《5.23抗疟计划》付诸实施,在全国多个研究单位协作下,组织植物化学与药理学等专业200多人,搜寻对抗耐氯喹恶性疟疾的新药.他们追索我国历代抗疟方剂,用约200种草药制成380多种抽提物,再筛查其对小鼠疟疾模型的疗效.最后确定,在60℃用乙醚萃取中药青蒿的黄花蒿所得第191号中性抽提物,对感染鼠疟和猴疟的小鼠与猴以及21例恶性疟、间日疟患者均能奏效.1972年11月,从该抽提物分离出相对分子质量0.282 kD的无色结晶,命名为青蒿素.它属于一种新型的倍半萜内酯.继后青蒿素纯品的胶囊被用于临床数千例疟疾患者.2006年以来,为克服耐药性,世界卫生组织(WHO)宣布改用青蒿素的联合疗法(ACT),挽救了80个国家100多万人的生命.因在发现青蒿素过程中的关键作用,屠呦呦被授予2011年度拉斯克临床医学研究奖.本文对青蒿素发现的争议,如何恰当评价其他科学家的贡献,以及开发植物界以外青蒿素新药源的近况,均作了简要报道.     

长学制医学微生物学实验教学体系构建

针对目前医学微生物学实验教学中的突出问题,从实验内容和实验教学手段等方面入手,探索建立一整套适用于七年制及长学制学生的实验课程教学体系,体现创新教育教学的理念.     

Non-invasive diagnosis of cutaneous leishmaniasis by the direct boil loop-mediated isothermal amplification method and MinION™ nanopore sequencing

Cutaneous leishmaniasis (CL) is gaining attention as a public health problem. We present two cases of CL imported from Syria and Venezuela in Japan. We diagnosed them as CL non-invasively by the direct boil loop-mediated isothermal amplification method and an innovative sequencing method using the MinION? sequencer. This report demonstrates that our procedure could be useful for the diagnosis of CL in both clinical and epidemiological settings.     

病原生物学专业本科生创新型人才培养中的生物安全问题

探讨病原生物学专业在医学本科生创新型人才培养过程中的生物安全问题。通过实验前的生物安全教育、实验进程中的规范操作以及实验之外的管理体系建设3个方面全程监管实验室生物安全, 以保障本科生参加科研实验的安全性。     

不同层次医学生实验室生物安全课程的教学实践与体会

根据对不同层次和专业医学生实验室生物安全教学的实践和体会,从教学指导思想、课程设置、考核评估等方面进行了总结,并分析了教学过程发现的问题,以期通过教学活动培养学生良好的实验室生物安全意识和素质。     

Simple But Efficacious Enrichment of Integral Membrane Proteins and Their Interactions for In-Depth Membrane Proteomics

Membrane proteins play essential roles in various cellular processes, such as nutrient transport, bioenergetic processes, cell adhesion, and signal transduction. Proteomics is one of the key approaches to exploring membrane proteins comprehensively. Bottom–up proteomics using LC–MS/MS has been widely used in membrane proteomics. However, the low abundance and hydrophobic features of membrane proteins, especially integral membrane proteins, make it difficult to handle the proteins and are the bottleneck for identification by LC–MS/MS. Herein, to improve the identification and quantification of membrane proteins, we have stepwisely evaluated methods of membrane enrichment for the sample preparation. The enrichment methods of membranes consisted of precipitation by ultracentrifugation and treatment by urea or alkaline solutions. The best enrichment method in the study, washing with urea after isolation of the membranes, resulted in the identification of almost twice as many membrane proteins compared with samples without the enrichment. Notably, the method significantly enhances the identified numbers of multispanning transmembrane proteins, such as solute carrier transporters, ABC transporters, and G-protein–coupled receptors, by almost sixfold. Using this method, we revealed the profiles of amino acid transport systems with the validation by functional assays and found more protein–protein interactions, including membrane protein complexes and clusters. Our protocol uses standard procedures in biochemistry, but the method was efficient for the in-depth analysis of membrane proteome in a wide range of samples.     

地方医科大学实验动物管理工作水平评价指标体系的构建

目的构建地方医科大学实验动物管理工作水平评价指标体系,为高校实验动物管理工作的评价提供参考。方法根据研究主题确定咨询专家人选37人,采用Delphi法进行问卷调查和统计分析。结果两轮咨询问卷回收率分别为70．27％和76．92％。权威系数为0．855;第二轮指标体系的协调系数为0．486。结论本次研究构成的地方医科大学实验动物管理工作水平评价指标体系是可靠的。     

The physico-chemical mechanism of mediated transport. I. Facilitated diffusion

On the basis of the currently accepted model for the cell membrane structure, a physico-chemical model for mediated transport is developed and solved for the case of polar non-electrolyte migration through the cell membrane. The model considers the interstitial space defined by the transport protein subunits to be the migration pathway for polar solutes. A Langmuir-type adsorption equilibrium is assumed at the interfaces and a multicomponent diffusion mechanism of solute and water is postulated within the migration pathway, where the polar residues of the transport protein represent another component of the system. Membrane selectivity is governed by the adsorption constants, which are shown to affect strongly the kinetics of transport. Isosmotic transport and the volume change of the cell are important features incorporated in the model, which is shown to fulfill the peculiar properties of facilitated diffusion systems. It is concluded that the same type of pathway can be used for the transport of other polar solutes through existing or induced hydrophilic channels, for which a similar approach is suggested.