Metabolomics analysis of multidrug-resistant breast cancer cells in vitro using methyl-tert-butyl ether method

The comprehensive characterization of metabolome and lipidome to reveal unknown pathological conditions, are being used to investigate the molecular mechanisms of cancer, especially in the field of early diagnosis, treatment, and prognosis. The multidrug resistance (MDR) of tumor cells limits the therapeutic effect of anti-cancer drugs and is the main obstacle for chemotherapy. Here, we adopted a methyl-tert-butyl ether (MTBE)-based extraction method to simultaneously extract small polar molecules and lipophilic metabolites for nontargeted metabolomics of multidrug-resistant breast cancer cell line MCF-7/ADR and its parental cell line MCF-7/S by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Distinctly different metabolic features were shown between MCF-7/ADR cells and MCF-7/S on the basis of multivariate analyses. 17 potential biomarkers were identified. And these potential biomarkers were mainly correlated with cell membrane lipids composition, cell signaling regulated by lipids, and anti-oxidation ability. The studies of cellular ultrastructure and morphology by in situ atomic force microscopy (AFM) also demonstrated the cellular membrane changed along with the MDR. We expect that this study could provide a new method for monitoring drug resistance during clinical chemotherapy and be useful for the development of drugs to overcome the MDR.

MTBE-based cellular lipidomics to investigate the mechanisms of multidrug resistance of breast cancer.     

城市固体废物产生量与经济增长脱钩关系的实证研究——以北京市为例

采用脱钩理论的3种评价方法 (脱钩指数法、IPAT模型法以及弹性分析法)对北京市城市固体废物产生量与经济增长之间的状态进行对比分析,发现:3种评价方法的原理不同,但评价结果基本一致,但Tapio(2005)提出的弹性分析法模型在指标细分上存在问题;北京市1979—2011年城市固体废物产生量总体实现相对脱钩,但通过分析个别年份状态数据发现要真正实现城市固体废物的减量化需要管理制度的改进,以及市民环保素质的提升。     

细胞外信号调节激酶在糖尿病大鼠肺病变中的作用

目的　观测糖尿病大鼠肺组织的病理改变及蛋白激酶C、胞外调节蛋白激酶活性的变化 ,探讨细胞信号传导系统在糖尿病大鼠肺病变中的作用。方法　制作糖尿病大鼠模型 ,4w后应用透射电镜观察大鼠肺组织病理改变 ,采用改良的Takay法测定蛋白激酶C活性 ,同位素法及蛋白质免疫印迹分析方法检测胞外调节蛋白激酶在糖尿病大鼠肺组织表达的变化。结果　糖尿病大鼠 4w肺组织病理改变为毛细血管基底膜及Ⅱ型肺泡上皮细胞基底膜不同程度增厚 ,肺间质胶原成份增多 ,蛋白激酶C、胞外调节蛋白激酶在肺组织活性增强。结论　链脲菌素糖尿病大鼠肺组织高糖环境下细胞内信号传导系统被激活 ,可能参与了糖尿病肺部并发症的发生和发展     

晚期日本血吸虫病肝组织学与肝纤维化指标的相关性研究

目的探讨晚期血吸虫病(晚血)血清肝纤维化指标及其肝组织内的表达与肝纤维化检查的肝组织病理活检的相关程度。方法肝组织手术活检标本经10%甲醛固定,常规石蜡包埋切片,HE染色,光镜下病理学检查。肝组织基质金属蛋白酶-1(MMPS-1)、基质金属蛋白酶组织抑制因子-1(TIMPS-1)、转化生长因子-β1(TGF-β1)采用免疫组化染色S-P法。血清MMPS-1、TGF-β1检测采用酶联免疫吸附试验(ELISA)法,TIMPS-1检测采用免疫透射比浊法。结果共检测晚血脾切除患者45例。肝组织病理学检查按Scheuer分级S13例(6.0%)、S25例(11.1%)、S319例(42.2%)、S418例(40.0%)。肝组织免疫组化MMPS-1“ ”27例(60.0%),“ ”10例(22.2%),“ ”1例(2.2%);TIMPS-1“ ”8例(17.8%),“ ”18例(40.0%),“ ”13例(28.9%)。TGF-β1“ ”8例(17%),“ ”22例(48.9%),“ ”10例(22.2%)。血清MMPS-1、TIMPS-1、TGF-β1含量除MMPS-1外,均随肝纤维化程度加重和免疫组化阳性表达强度的增强而增高。结论晚血肝组织病理学检查肝纤维化程度的加重与肝组织TIMPS-1、TGF-β1免疫组化阳性表达强度及血清含量呈正相关;检测血清TIMPS-1、TGF-β1含量及TIMPS-1/MMPS-1比值是肝纤维化诊断和疗效评价较好的无创伤性指标。     

苦瓜蛋白对柯萨奇B3病毒性心肌炎小鼠半胱天冬酶3活性及凋亡的抑制作用

为研究苦瓜蛋白对凋亡的关键酶半胱天冬酶 3及凋亡的调节作用 ,用已经建立起来的方法从苦瓜果肉中提取苦瓜蛋白。将BALB/C小鼠分为 4组 :病毒对照组、正常对照组、药物对照组和药物治疗组 ,分别在第 0天、第 3天、第 7天和第 14天各处死 5只小鼠 ,第 2 1天全部处死动物 ,心肌组织半胱天冬酶 3活性测定按照CAL BIOCHEM公司的试剂说明书进行 ,并稍加改正 ,凋亡鉴定按照Oncogene公司的TdT DNA裂解片断末端原位标记试剂说明书进行。结果发现 ,①病毒对照组第 7天开始出现半胱天冬酶 3活性 (0 .6 3± 0 .2 1pmol/min ,n =5 ) ,第 14天的活性 (10 .9± 1.5pmol/min ,n =5 )显著高于第 7天 ,第 2 1天的活性 (12 .6± 1.3pmol/min ,n =5 )又高于第 14天。②药物治疗组 ,只有一个第 2 1天的标本有半胱天冬酶 3活性 (0 .4 1pmol/min) ,其它两组均未检测到此酶的活性。③DNA裂解片断末端原位标记法发现 ,病毒对照组在第 7天心肌中有少数细胞凋亡 ,第 14天、第 2 1天凋亡细胞明显增多 ,在非病变区域可发现单个凋亡的心肌细胞。治疗组未发现凋亡细胞 ,其它两组也未发现凋亡细胞。结果提示 ,CVB3病毒性心肌炎中发现有明显的凋亡现象 ,凋亡和半胱天冬酶 3发现于第 7天 ,且随着时间增加而逐渐加重(增强 ) ;苦瓜蛋白可显     

乐胃煎逆转胃癌前病变AgNOR及细胞图像分析

目的研究乐胃煎逆转胃癌前病变不完全结肠型肠化和／或中度异型增生的疗效．方法胃镜病理证实为不完全结肠型肠化和／或中度异型增生４６例．治疗组３０例用乐胃煎，对照组１６例用德诺（Ｄｅ＿Ｎｏｌ）．治疗前后胃镜活检胃窦固定部位粘膜标本作ＡｇＮＯＲ染色及细胞图像分析．结果乐胃煎对不完全结肠型肠化及中度异型增生总有效率均高于Ｄｅ＿Ｎｏｌ，分别为７２％比２５％（Ｐ＜００５）和８９５％比４４４％（Ｐ＜００５）．乐胃煎治疗前后，ＡｇＮＯＲ计数分别为７３０±１１６和４８１±１５０（Ｐ＜００１），Ｄｅ＿Ｎｏｌ组为７７３±０９２和７０５±１０２（Ｐ＜００１）．两组治疗前后ＡｇＮＯＲ计数差值均数相比，统计学上也有显著性差异，分别为２５２±１５４和０６９±０４８（Ｐ＜００１）．乐胃煎组中２０例作细胞图像分析，治疗后各参数（长轴、短轴、核浆比、结构异型指数等）均有不同程度的降低，有显著性差异．结论乐胃煎确有较好地逆转胃癌前病变的功效．     

Green and facile edge-oxidation of multi-layer graphene by sodium persulfate activated with ferrous ions

Effective edge oxidation of graphene with high structural integrity is highly desirable yet technically challenging for most practical applications. In this work, we have developed a green and facile strategy to obtain edge-oxidized graphene with good dispersion stability and high electrical conductivity by exploiting high edge reactivity of highly conductive multi-layer graphene and oxidizing radicals (SO₄⁻˙) generated from sodium persulfate (Na₂S₂O₈) with ferrous ion (Fe²⁺) activation. Owing to high structural integrity of pristine graphene and effective edge oxidation, the obtained edge-oxidized graphene exhibited excellent dispersion stability and satisfactory electrical conductivity (i.e. ≥240 S cm⁻¹). Moreover, the oxidation degree of pristine graphene can be well controlled by adjusting treatment time. The obtained edge-oxidized graphene is expected to find a variety of applications in many fields of anti-static films, energy storage materials, flexible sensors and high-performance nanocomposites.

A green and facile strategy is represented to obtain edge-oxidized graphene by exploiting sulfate radicals generated from Na₂S₂O₈ with Fe²⁺ activation.     

Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures

Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential- colony forming cells [HPP-CFC], long-term culture-initiating cells [LTC- IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit-megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40- fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment.     

Shp2 deletion in hepatocytes suppresses hepatocarcinogenesis driven by oncogenic β-Catenin,PIK3CA and MET

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