Serum proteomic profiling for the early diagnosis of colorectal cancer

No ideal serum biomarker currently exists for the early diagnosis of colorectal cancer (CRC). Magnetic bead‐based fractionation coupled with MALDI‐TOF MS was used to screen serum samples from CRC patients, healthy controls, and other cancer patients. A diagnostic model with five proteomic features (m/z 1778.97, 1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with best performance. The Fisher‐based model could discriminate CRC patients from the controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test set. We further validated the model with 94.4% (254/269) sensitivity and 75.5% (83/110) specificity in the external independent group. In other cancers group, the Fisher‐based model classified 25 of 46 samples (54.3%) as positive and the other 21 as negative. With FT‐ICR‐MS, the proteomic features of m/z 1778.97, 1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in CRC, were identified as fragments of complement C3f. Therefore, the Fisher‐based model containing five proteomic features was able to effectively differentiate CRC patients from healthy controls and other cancers with a high sensitivity and specificity, and may be CRC‐specific. Serum complement C3f, which was significantly decreased in CRC group, may be relevant to the incidence of CRC. J. Cell. Biochem. 114: 448–455, 2013. © 2012 Wiley Periodicals, Inc.     

Nuclear magnetic resonance structure of the P395S mutant of the N-SH2 domain of the p85 subunit of PI3 kinase: an SH2 domain with altered specificity

Understanding the specificity of Src homology 2 (SH2) domains is important because of their critical role in cell signaling. Previous genetic analysis has characterized mutants of the N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K). The P395S mutant exhibits a specificity for phosphopeptide binding different from that of the wild-type SH2. The P395S mutant has an increased affinity for the platelet-derived growth factor receptor (PDGFr) compared to polyomavirus middle T antigen (MT). Solution structures of the P395S mutant of the p85 N-SH2 alone and complexed to a PDGFr phosphopeptide were determined to explain the change in specificity. Chemical shift perturbations caused by different peptides were compared for mutant and wild-type structures. The results show that the single P395S mutation has broad effects on the structure. Furthermore, they provide a rationale for the observed changes in binding preference.     

Hsp90 inhibitor 17-AAG sensitizes Bcl-2 inhibitor (-)-gossypol by suppressing ERK-mediated protective autophagy and Mcl-1 accumulation in hepatocellular carcinoma cells

Natural BH3-memitic (-)-gossypol shows promising antitumor efficacy in several kinds of cancer. However, our previous studies have demonstrated that protective autophagy decreases the drug sensitivities of Bcl-2 inhibitors in hepatocellular carcinoma (HCC) cells. In the present study, we are the first to report that Hsp90 inhibitor 17-AAG enhanced (-)-gossypol-induced apoptosis via suppressing (-)-gossypol-triggered protective autophagy and Mcl-1 accumulation. The suppression effect of 17-AAG on autophagy was mediated by inhibiting ERK-mediated Bcl-2 phosphorylation while was not related to Beclin1 or LC3 protein instability. Meanwhile, 17-AAG downregulated (-)-gossypol-triggered Mcl-1 accumulation by suppressing Mcl-1^Thr163 phosphorylation and promoting protein degradation. Collectively, our study indicates that Hsp90 plays an important role in tumor maintenance and inhibition of Hsp90 may become a new strategy for sensitizing Bcl-2-targeted chemotherapies in HCC cells.     

酒醅来源酵母菌合成异戊醇能力与途径解析

【背景】异戊醇是酵母菌在白酒发酵过程中通过氨基酸合成代谢途径和氨基酸分解代谢途径合成的主要高级醇,其含量影响白酒饮用的舒适度。【目的】分析和比较分离自浓香型白酒酒醅中的酵母菌合成异戊醇的能力,揭示酵母菌合成异戊醇的途径。【方法】从酒醅中分离具有异戊醇合成能力的酵母菌株,比较不同生长时期酵母菌合成异戊醇的能力,通过前体物代谢分析它们合成异戊醇的途径。【结果】分离自酒醅的5株酵母的异戊醇合成能力从强到弱依次为Naumovozyma castellii JP3-1、Saccharomyces cerevisiae JP3、Pichia fermentans JP22、Pichia kudriavzevii JP1和Naumovozyma dairenensis CBS421。这些酵母合成异戊醇的时期主要在对数生长期,N. castellii JP3-1、P. fermentans JP22和N. dairenensis CBS421在稳定生长期也合成异戊醇。S. cerevisiae JP3、N. castellii JP3-1和N. dairenensis CBS421在整个生长时期主要通过Harris途径合成异戊醇;P. kudriavzevii JP1在整个时期主要通过Ehrlich途径合成异戊醇;P. fermentans JP22在对数生长期通过Harris途径和Ehrlich途径合成异戊醇的能力接近,在稳定生长期主要通过Harris途径合成异戊醇。【结论】本研究揭示了酒醅来源5个属种酵母合成异戊醇的途径、能力与其生长时期的关系,研究结果可为解析浓香型白酒发酵过程异戊醇合成、积累机制及实施白酒发酵过程异戊醇合成的精准调控提供理论依据。     

2001-2019年台风干扰下我国东南沿海地区植被抵抗力和恢复力评估

台风是影响我国陆地生态系统结构和功能的主要自然灾害之一,尤其对东南沿海地区植被具有明显的干扰效应。为深入了解台风对我国沿海地区植被的影响及其响应,基于MODIS增强型植被指数(Enhanced Vegetation Index, EVI)和叶面积指数(Leaf Area Index, LAI),分析了2001-2019年间不同等级的台风对植被EVI和LAI的影响,评估台风登陆时植被的抵抗力及台风过后植被的恢复力。结果表明:(1)2001-2019年间,共有70个台风登陆我国东南沿海地区,其中,台风(TY)、强台风(STY)与超强台风(SuperTY)的数量分别为35、26和9个。我国台湾省的台风登陆次数最多,为26个,其次为广东省(20个);(2)在整个研究区范围内,台风(TY)、强台风(STY)与超强台风(SuperTY) 登陆后的EVI净变化率分别为4.88%、-7.48%、-1.85%,LAI净变化率分别为22.28%、-65.70%、-17.60%;(3)在经历台风干扰后,沿海地区大部分植被可在3个月之内得到恢复,其中浙江省与广东省植被的恢复时间较长,海南省与台湾省植被的恢复时间较短。研究结果对我国沿海地区森林经营管理和生态环境保护具有重要意义。     

定点突变提高枯草芽孢杆菌角蛋白酶的低温催化活性

[背景]角蛋白酶KerZ1能在60℃的最适温度下高效降解角蛋白底物,然而其在低于最适温度条件下的酶活极低,难以适应工业生产和实际应用的要求.[目的]提升角蛋白酶KerZ1的低温催化活性.[方法]结合同源比对与折叠自由能分析向角蛋白酶KerZ1引入氨基酸突变,并对突变体的酶学性质进行研究.[结果]对KerZ1柔性环区域(...     

Insights into the antineoplastic mechanism of Chelidonium majus via systems pharmacology approach

Background: The antineoplastic activity of Chelidonium majus has been reported, but its mechanism of action (MoA) is unsuspected. The emerging theory of systems pharmacology may be a useful approach to analyze the complicated MoA of this multi-ingredient traditional Chinese medicine (TCM). Methods: We collected the ingredients and related compound-target interactions of C. majus from several databases. The bSDTNBI (balanced substructure-drug-target network-based inference) method was applied to predict each ingredient’s targets. Pathway enrichment analysis was subsequently conducted to illustrate the potential MoA, and prognostic genes were identified to predict the certain types of cancers that C. majus might be beneficial in treatment. Bioassays and literature survey were used to validate the in silico results. Results: Systems pharmacology analysis demonstrated that C. majus exerted experimental or putative interactions with 18 cancer-associated pathways, and might specifically act on 13 types of cancers. Chelidonine, sanguinarine, chelerythrine, berberine, and coptisine, which are the predominant components of C. majus, may suppress the cancer genes by regulating cell cycle, inducing cell apoptosis and inhibiting proliferation. Conclusions: The antineoplastic MoA of C. majus was investigated by systems pharmacology approach. C. majus exhibited promising pharmacological effect against cancer, and may consequently be useful material in further drug development. The alkaloids are the key components in C. majus that exhibit anticancer activity.     

Growth Simulation and Discrimination of Botrytis cinerea,Rhizopus stolonifer and Colletotrichum acutatum Using Hyperspectral Reflectance Imaging

This research aimed to develop a rapid and nondestructive method to model the growth and discrimination of spoilage fungi, like Botrytis cinerea, Rhizopus stolonifer and Colletotrichum acutatum, based on hyperspectral imaging system (HIS). A hyperspectral imaging system was used to measure the spectral response of fungi inoculated on potato dextrose agar plates and stored at 28°C and 85% RH. The fungi were analyzed every 12 h over two days during growth, and optimal simulation models were built based on HIS parameters. The results showed that the coefficients of determination (R²) of simulation models for testing datasets were 0.7223 to 0.9914, and the sum square error (SSE) and root mean square error (RMSE) were in a range of 2.03–53.40×10⁻⁴ and 0.011–0.756, respectively. The correlation coefficients between the HIS parameters and colony forming units of fungi were high from 0.887 to 0.957. In addition, fungi species was discriminated by partial least squares discrimination analysis (PLSDA), with the classification accuracy of 97.5% for the test dataset at 36 h. The application of this method in real food has been addressed through the analysis of Botrytis cinerea, Rhizopus stolonifer and Colletotrichum acutatum inoculated in peaches, demonstrating that the HIS technique was effective for simulation of fungal infection in real food. This paper supplied a new technique and useful information for further study into modeling the growth of fungi and detecting fruit spoilage caused by fungi based on HIS.     

蛋白质环化的研究进展

天然蛋白质在生物体内主要以线性形式存在,由于多数蛋白质(酶)热稳定性较差,制约了其在工业催化、食品制造、医药领域的高效应用。自然界中发现的天然环肽类物质具有首尾相连的环化结构,使蛋白质具有较高的稳定性,为改造酶的结构、提高其热稳定性及拓宽其应用范围提供了新思路。本文根据国内外在蛋白质环化领域的新动态并结合本实验室的研究,系统介绍了内含肽介导的蛋白质反式剪接、表达蛋白连接、转肽酶催化的转肽作用等几种传统蛋白质环化方法,着重介绍了基于新型超强分子粘合剂Spy Tag/Spy Catcher介导的蛋白质环化的研究。     

遗传性共济失调症家系手纹分析

本文报道了河南省永城县一遗传性共济失调症家系(汉族)的手纹,收集到手纹样本70人,与汉族正常人比较,该家系尺箕偏低,弓型纹较高(P<0.01);掌褶普通型少,而通贯型和过渡I型多(P<0.01);atd角偏大;指三叉c主线至7、9区者出现率高(P<0.01)。