Targeting to overexpressed glucose-regulated protein 78 in gastric cancer discovered by 2D DIGE improves the diagnostic and therapeutic efficacy of micelles-mediated system

The survivals of gastric cancer (GC) patients are associated with early diagnosis and effective treatments. Therefore, it is urgent for the discovery of early GC biomarkers and tumor-targeting therapeutics. The aim of this study was to uncover putative tissue biomarkers of GC using 2D DIGE and then apply one of these specific markers in GC treatment. We found three putative biomarkers of GC with significant differences in expression level compared to adjacent normal tissue, including glucose-regulated protein 78 (GRP78) and glutathione s-transferase pi (GSTpi) with increased expression level, and alpha-1 antitrypsin (A1AT) with reduced expression level. The overexpressed GRP78 was used as a targeted protein for guiding the drugs to tumor cells, leading to more effective treatment for GC xenografts. Our results demonstrated that the designated GRP78-binding peptide based on the sequence, WIFPWIQL, was selectively prone to recognize and bind to GC MKN45 cells in vitro, and also improve the delivery efficiency of polymeric micelles-encapsulated drugs into tumor cells and displayed better therapeutic outcome in experimental animals. This strategy of GRP78-mediated drug targeting system may bring chemotherapeutic drugs with more precise targeting to tumor cells, leading to minimize side effects on patients after chemotherapy.     

Synthesis and Activity Evaluation of Nasopharyngeal Carcinoma Inhibitors Based on 6‐(Pyrimidin‐4‐yl)‐1H‐indazole

Human nasopharyngeal carcinoma is a common head and neck malignancy with high incidence in Southeast Asia and Southern China. It is necessary to develop safe, effective and inexpensive anticancer agents to improve the therapeutics of patients with nasopharyngeal carcinoma. A series of small molecular compounds based on 6‐(pyrimidin‐4‐yl)‐1H‐indazole were synthesized and evaluated for antiproliferative activities against human nasopharyngeal carcinoma cell lines SUNE1. Compounds 6b , 6c , 6e and 6l showed potent antiproliferative activities similar to positive control drug cisplatin in vitro with lower nephrotoxicity than it. N‐[4‐(1H‐Indazol‐6‐yl)pyrimidin‐2‐yl]benzene‐1,3‐diamine ( 6l ) was selected for further study. It was found that 6l induced mitochondria‐mediated apoptosis and G₂/M phase arrest in SUNE1 cells. Furthermore, compound 6l at 10 mg/kg can suppress the growth of an implanted SUNE1 xenograft with a TGI% (tumor growth inhibition) value of 50 % and did not cause serious side effects in BALB/c nude mice. This study suggests that 6‐(pyrimidin‐4‐yl)‐1H‐indazole derivatives are a series of small molecule compounds with anti‐nasopharyngeal carcinoma activities.     

Nicotinate-Curcumin Impedes Foam Cell Formation from THP-1 Cells through Restoring Autophagy Flux

Our previous studies have indicated that a novel curcumin derivate nicotinate-curcumin (NC) has beneficial effects on the prevention of atherosclerosis, but the precise mechanisms are not fully understood. Given that autophagy regulates lipid metabolism, the present study was designed to investigate whether NC decreases foam cell formation through restoring autophagy flux in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells. Our results showed that ox-LDL (100 μg/ml) was accumulated in THP-1 cells and impaired autophagy flux. Ox-LDL-induced impairment of autophagy was enhanced by treatment with the autophagy inhibitor chloroquine (CQ) and rescued by the autophagy inducer rapamycin. The aggregation of ox-LDL was increased by CQ, but decreased by rapamycin. In addition, colocalization of lipid droplets with LC3-II was remarkably reduced in ox-LDL group. In contrast, NC (10 μM) rescued the impaired autophagy flux by significantly increasing level of LC3-II, the number of autophagolysosomes, and the degradation of p62 in ox-LDL-treated THP-1 cells. Inhibition of the PI3K-Akt-mTOR signaling was required for NC-rescued autophagy flux. Notably, our results showed that NC remarkably promoted the colocalization of lipid droplets with autophagolysosomes, increased efflux of cholesterol, and reduced ox-LDL accumulation in THP-1 cells. However, treatment with 3-methyladenine (3-MA) or CQ reduced the protective effects of NC on lipid accumulation. Collectively, the findings suggest that NC decreases lipid accumulation in THP-1 cells through restoring autophagy flux, and further implicate that NC may be a potential therapeutic reagent to reverse atherosclerosis.     

长萼兰花蕉(Orchidantha chinensis var.longisepala)的繁育系统研究

通过野外观察并采用杂交指数（OCI）测定、花粉/胚珠比（P/O）检测、人工控制授粉等方法,对长萼兰花蕉（Orchidantha chinensis var.longisepala（D.Fang） T.L.Wu）种群的繁育系统进行了研究,采用常规石蜡切片与扫描电子显微镜（SEM）观察了柱头与"V"形黏盘的结构与形态。结果表明,长萼兰花蕉单花花期一般为18 d,依其花部形态的变化可分为蕾期、花萼未反转期、花萼反转期、唇瓣枯萎期、花萼枯萎期5个时期;根据杂交指数值为4、P/O值为253.89 ±21.09、人工异花授粉结实率分别为45%（2014年）和75%（2015年）,显示出长萼兰花蕉的繁育系统属于异交,且需要传粉者。石蜡切片观察到长萼兰花蕉黏盘区与柱头可授区之间是光滑的表皮细胞,结合人工授粉实验与分泌物含糖量测定结果表明,长萼兰花蕉的"V"形黏盘不具有可授性,其作用可能是分泌黏液附着在传粉者背部使其便于携带花粉。长萼兰花蕉整个花期环境湿冷、多雨且开花同步性较低,这些因素很可能造成其有效传粉媒介缺乏,影响了传粉成功;另一方面,长萼兰花蕉有性繁殖受到限制,其主要通过根状茎进行无性繁殖后代,所以分布范围比较狭窄。     

Inside Back Cover: Development of a 3‐dimensional tissue lung phantom of a preterm infant for optical measurements of oxygen—Laser‐detector position considerations (J. Biophotonics 3/2018)

The picture depicts the different 3d‐printed organs, thorax, lungs, heart and bone. Assembled it is used as an optical phantom of a preterm infant for performing percutaneous optical measurements of the gas content in the lungs. In order to simulate the optical properties of the tissue, the heart and thorax can be filled with liquid phantoms, a mixture of Intralipid and Indian Ink. Further details can be found in the article by Jim Larsson et al. ( e201700097 ).

     

神经递质的可视化荧光检测技术研究进展

神经递质是神经系统中至关重要的组成部分,神经递质释放的时间和空间变化是神经网络中信息处理的核心,可视化监测神经递质的生物传感器是探究各类生理和病理活动的重要工具。文中综述了近年来具有较高时间和空间分辨率的监测神经递质时空分布变化技术的研究进展,介绍了对谷氨酸、多巴胺、γ-氨基丁酸和乙酰胆碱这4类重要的神经递质的检测方法,并归纳总结了各类检测方法的基本原理和优缺点,为设计具有高时空分辨率的神经递质传感器提供一个较为系统的参考。     

Different Glycosylation in Acetylcholinesterases from Mammalian Brain and Erythrocytes

Acetylcholinesterases (EC 3.1.1.7, AChE) have varying amounts of carbohydrates attached to the core protein. Sequence analysis of the known primary structures gives evidence for several asparagine-linked carbohydrates. From the differences in molecular mass determined on sodium dodecyl sulfate-polyacrylamide gel before and after deglycosylation with N-glycosidase F (EC 3.2.2.18), it is seen that dimeric AChE from red cell membranes is more heavily glycosylated than the tetrameric brain enzyme. Furthermore, dimeric and tetrameric forms of bovine AChE are more heavily glycosylated than the corresponding human enzymes. Monoclonal antibodies 2E6, 1H11, and 2G8 raised against detergent-soluble AChE from electric organs of Torpedo nacline timilei as well as Elec-39 raised against AChE from Electrophorus electricus cross-reacted with AChE from bovine and human brain but not with AChE from erythrocytes. Treatment of the enzyme with N-glycosidase F abolished binding of monoclonal antibodies, suggesting that the epitope, or part of it, consists of N-linked carbohydrates. Analysis of N-acetylglucosamine sugars revealed the presence of N-acetylglucosamine in all forms of cholinesterases investigated, giving evidence for N-linked glycosylation. On the other hand, N-acetylgalactosamine was not found in AChE from human and bovine brain or in butyrylcholinesterase (EC 3.1.1.8) from human serum, indicating that these forms of cholinesterase did not contain O-linked carbohydrates. Despite the notion that within one species, the different forms of AChE arise from one gene by different splicing, our present results show that dimeric erythrocyte and tetrameric brain AChE must undergo different postsynthetic modifications leading to differences in their glycosylation patterns.