巨噬细胞集落刺激因子与动脉粥样硬化

巨噬细胞集落刺激因子与动脉粥样硬化欧阳谦,周玫,陈瑗（第一军医大学自由基医学研究室,广州５１０５１５）关键词巨噬细胞集落刺激因子,氧化修饰低密度脂蛋白,动脉粥样硬化巨噬细胞集落刺激因子（ＭＣＳＦ）是一种多肽类激素样造血生长因子,可由单核细胞、巨噬细胞...     

粒细胞-巨噬细胞集落刺激因子微球制剂的体外释放研究

目的：开发一种粒细胞-巨噬细胞集落刺激因子（GM—CSF）长效缓释微球剂型。方法：采用S／O／hO法制备了包裹粒细胞一巨噬细胞集落刺激因子多糖玻璃体颗粒的PLGA微球,考察了微球的表面形态、粒径分布等,并且运用ELISA方法考察了微球的体外释放效果。结果：本方法制备的粒细胞-巨噬细胞集落刺激因子微球光滑圆整,粒径分布均匀,体外可以缓释达32天,累积释放率接近90％。结论：本方法制备的粒细胞-巨噬细胞集落刺激因子微球能有效地保护蛋白活性,同时实现长效缓释的目标,是一种可行的蛋白缓释方案。     

聚乙二醇定点修饰重组人粒细胞集落刺激因子突变体的研究

研究了重组人粒细胞集落刺激因子突变体（rmhG-CSF）的聚乙二醇化修饰、分离纯化和活性鉴定。通过对人重组粒细胞集落刺激因子（rhG-CSF）第1,3,4,5,17位氨基酸进行突变,并在C末端加了一个半胱氨酸,获得了体外活性为原型rhG-CSF 150％以上的重组人粒细胞集落刺激因子突变体（rmhG-CSF）。然后用分子量为20kD的甲氧聚乙二醇马来酸酐（mPEG-Mal）修饰rmhG-CSF,反应混合物经离子交换和凝胶过滤柱纯化,得到纯化的聚乙二醇重组人粒细胞集落刺激因子突变体（PEG-rmhG-CSF）。SDS-PAGE电泳分析表明纯化后的PEG-rmhG-CSF的纯度大于95％,体外活性分析表明PEG-rmhG-CSF活性优于目前临床使用的聚乙二醇重组人粒细胞集落刺激因子（PEG-rhG-CSF,Neulasta^?）,药代动力学研究表明PEG-rmhG-CSF体内半衰期约为14h,比修饰前延长了7倍。     

培养大鼠主动脉血管平滑肌细胞产生巨噬细胞集落刺激因子及其受体的表达

本研究用培养大鼠主动脉血管平滑肌细胞（ＶＳＭＣｓ）,结果如下：（１）用生物活性检测法发现ＶＳＭＣｓ无血清条件培养液可刺激巨噬细胞集落形成,其作用能被抗巨噬细胞集落刺激因子（ＭＣＳＦ）抗体抑制;（２）用免疫细胞化学技术证明ＶＳＭＣｓ存在ＭＣＳＦ受体;（３）用Ｎｏｒｔｈｅｒｎ ｂｌｏｔ技术证明ＶＳＭＣｓ有ＭＣＳＦ及其受本的ｍＲＮＡ表达,血清刺激使两者表达明显增强。本研究首次报道了培养大鼠主动脉ＶＳＭＣ     

FL对脐血造血细胞长期液体培养的影响

用脐血进行干细胞移植有许多优点,但有一个主要的缺点是可获得的细胞数量有限,因此脐血干细胞的体外扩增对于其临床应用具有重要意义。考察了Ｆｌｔ－３配体（ＦＬ）和干细胞因子（ＳＣＦ）,白介素３（ＩＬ－３）,ＩＬ－６,粒细胞集落刺激因子（Ｇ－ＣＳＦ）,粒细胞巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）的组合对脐血细胞扩增和分化的影响,培养４２ｄ,总细胞最多扩增了３８５．３０±１６３．５１倍（ＦＬ＋ＳＣＦ＋Ｇ－ＣＳ     

毛喉萜对小鼠骨髓细胞和腹腔巨噬细胞表面胰岛素受体和GM－CSF受体的下调作用

放射性标记受体分析表明毛喉萜（ＦＳＫ）可以降低小鼠骨央细胞和腹腔巨噬细胞表面的胰岛素（ＩＮＳ）和粒细胞－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）受体数目,而且对ＧＭ－ＣＳＦ的作用有剂量和时间依赖性,经ＦＳＫ处理的巨噬细胞酸性磷酸酶活性增加,微丝更加舒展。     

大肠杆菌表达的重组人粒细胞—巨噬细胞集落刺激因子（rhGM—CS…

对重组人粒细胞－巨噬细胞集落刺激因子（ｒｈＧＭ－ＣＳＦ）的工程菌表达产物进行纯化,经过超声破碎,包涵体抽提,凝胶层析,复性,离子交换一系列纯化步骤,终产物纯度达９８％,比活性达１０００００００ｕ／ｍｇ。     

大肠杆菌表达的重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)的纯化

对重组人粒细胞－巨噬细胞集落刺激因子（ｒｈＧＭ－ＣＳＦ）的工程菌表达产物进行纯化,经过超声破碎,包涵体抽提,凝胶层析,复性,离子交换一系列纯化步骤,终产物纯度达９８％,比活性达１０００００００ｕ／ｍｇ。     

粒细胞-巨噬细胞集落刺激因子微球制剂治疗肿瘤的研究

目的：评价粒细胞－巨噬细胞集落刺激因子（GM—csF）微球剂型在肿瘤动物模型治疗作用。方法：建立肿瘤动物模型,微球剂型对该肿瘤模型治疗效果考察及毒性评价,同时与市售的注射水溶液剂型进行比较。结果：微球剂型和市售水溶液注射剂型同剂量对肿瘤模型治疗效果,微球剂型的效果明显好于市售的;同时微球剂型的毒性也小于市售的。结论：粒细胞－巨噬细胞集落刺激因子微球能提高GM—CSF治疗效果,同时降低毒性。     

FDA着手进行非专利生物技术药品等同_陛判断

欧洲有3种非专利生物技术药品[人生长激素、促红细胞生成素（EPO）、粒细胞巨噬细胞集落刺激因子（GM—CSF）]、日本有2种（人生长激素、促红细胞生成素）已经上市销售。但是,美国虽然已经确立了关于非专利生物技术药品批准制度的方针,但必要的法律制度和指南等尚不完备。围绕生物技术药品的这种环境差异源于美国食品与药物管理局（FDA）在判断专利生物技术药品和非专利生物技术药品之间的等同性上踌躇不决。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Synthesis and antimicrobial studies of hydrazone derivatives of 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid and 4-[3-(3,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78?µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.

     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).