Expansion of bone marrow IFN-alpha-producing dendritic cells in New Zealand Black (NZB) mice: high level expression of TLR9 and secretion of IFN-alpha in NZB bone marrow

Patients with systemic lupus erythematosus have elevated IFN-alpha production. Furthermore, sera IFN-alpha levels correlate with disease activity. We have focused our attention on whether this phenotype is also seen in the New Zealand Black (NZB) mice and simultaneously addressed the underlying mechanisms. Specifically, we analyzed: 1) levels of sera IFN-alpha after type A CpG ODN 2216 injection in autoimmunity-prone NZB and control mice, and 2) levels of IFN-alpha synthesized by IFN-alpha-producing dendritic cells (IPDCs) using highly enriched populations of CD11c+B220+ IPDCs derived from NZB and control mice; IPDCs are divided into two subpopulations (CD4+CD11c+B220+ and CD4-CD11c+B220+). Our data demonstrate that NZB mice produced higher levels of sera IFN-alpha after type A CpG ODN 2216 injection when compared with control mice (p < 0.01). In addition, the cell numbers, frequency, and TLR9 mRNA levels of CD4+ and CD4- IPDC were markedly increased in the bone marrow (BM) of NZB mice. Upon in vitro stimulation with TLR9 ligand-CpG ODN 2216, higher levels of IFN-alpha were synthesized by IPDCs from the BM of NZB. The major contributor of IFN-alpha was the CD4-CD11c+B220+ IPDC subpopulation. Furthermore, NZB BM IPDCs manifest impaired expression of homing chemokine CCR7 and CD62L, and IL-12 production. These data on the functional characteristics of the IPDC lineages explain in part the mechanism of hyper-IFN-alpha production and help clarify the mechanism for the expansion of NZB BM IPDCs.     

Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library

It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182–188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer.     

Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR‐mediated autophagy flux pathway

Human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes) have been implicated as a novel therapeutic approach for tissue injury repair and regeneration, but the effects of hucMSC‐exosomes on coxsackievirus B3 (CVB3)‐induced myocarditis remain unknown. The object of the present study is to investigate whether hucMSC‐exosomes have therapeutic effects on CVB3‐induced myocarditis (VMC). HucMSC‐exosomes were identified using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. The purified hucMSC‐exosomes tagged with PKH26 were tail intravenously injected into VMC model mice in vivo and used to administrate CVB3‐infected human cardiomyocytes (HCMs) in vitro, respectively. The effects of hucMSC‐exosomes on myocardial pathology injury, proinflammatory cytokines and cardiac function were evaluated through haematoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) and Doppler echocardiography. The anti‐apoptosis role and potential mechanism of hucMSC‐exosomes were explored using TUNEL staining, flow cytometry, immunohistochemistry, Ad‐mRFP‐GFP‐LC3 transduction and Western blot. In vivo results showed that hucMSC‐exosomes (50 μg iv) significantly alleviated myocardium injury, shrank the production of proinflammatory cytokines and improved cardiac function. Moreover, in vitro data showed that hucMSC‐exosomes (50 μg/mL) inhibited the apoptosis of CVB3‐infected HCM through increasing pAMPK/AMPK ratio and up‐regulating autophagy proteins LC3II/I, BECLIN‐1 and anti‐apoptosis protein BCL‐2 as well as decreasing pmTOR/mTOR ratio, promoting the degradation of autophagy flux protein P62 and down‐regulating apoptosis protein BAX. In conclusion, hucMSC‐exosomes could alleviate CVB3‐induced myocarditis via activating AMPK/mTOR‐mediated autophagy flux pathway to attenuate cardiomyocyte apoptosis, which will be benefit for MSC‐exosome therapy of myocarditis in the future.     

c—fos,c—myb和c—erbB—2与大鼠卵巢颗粒细胞生孕酮调？…

目的和方法：用离体细胞体外孵育法,观察肥义ｃ－ｆｏｓ、ｃ－ｍｙｂ和ｃ－ｅｒｂＢ－２寡脱氧核苷酸（ｃ－ｆｏｓ ＯＤＮ、ｃ－ｍｙｂ ＯＤＮ和ｃ－ｅｒｂＢ－２ ＯＤＮ）对ｈＣＧ诱导大鼠颗粒细胞孕酮产生的影响。同时观察内皮素－１、γ－氨基丁酸和钙离子通道阻断剂维拉帕米对细胞中ｃ－ｆｏｓ、ｃ－ｍｙｂ和ｃ－ｅｒｂＢ－２蛋白的影响。结果：反义ｃ－ｆｏｓ、ｃ－ｍｙｂ和ｃ－ｅｒｂＢ－２ ＯＤＮ均明显抑制ｈＣＧ诱导颗     

植物干细胞培养研究进展

植物干细胞位于分生组织,是处于未分化状态的细胞,液泡化程度低,具有较高的线粒体活性,遗传稳定,具有很强的自我更新和再生能力。植物干细胞培养在下游制药和功能性食品以及化妆品行业具有广泛的应用潜质。文中综述了植物干细胞的基本培养技术、鉴别技术,为该领域的深入研究提供参考。     

亚硝酸盐氮对凡纳滨对虾毒性和抗病相关因子影响

用常规生物毒性实验方法,在不同盐度下进行亚硝酸盐氮对凡纳滨对虾的急性毒性实验;并加亚硝酸盐氮于凡纳滨对虾的养殖环境中,检测与抗病力相关因子的变化。研究亚硝酸盐氮对凡纳滨对虾的毒性和抗病力相关因子的影响。结果表明:盐度对亚硝酸盐氮的毒性有较大影响。盐度为31时,24hLC50、48hLC50、72hLC50和96hLC50分别为314.9mg/L1、75.3mg/L1、00.2mg/L和89.0mg/L;盐度为17时,分别为132.3mg/L、65.6mg/L、51.3mg/L和39.5mg/L。盐度31实验组的亚硝酸盐氮半致死浓度均显著(P<0.05)高于盐度17实验组。在低盐度条件下亚硝酸盐氮的毒性较强。亚硝酸盐氮对凡纳滨对虾抗病力相关因子有显著的影响。亚硝酸盐氮浓度为4.0mg/L和8.0mg/L时,其血细胞数、超氧化物歧化酶(SOD)活力、酚氧化酶(PO)活力、抗菌活力(Ua)、溶菌活力(UL)和血清蛋白含量均显著(P<0.05)低于对照组;不吸污组抗病力相关因子活性均显著(P<0.05)低于吸污组。低浓度的亚硝酸盐氮可降低凡纳滨对虾抗病能力,亚硝酸盐氮浓度越高,其抗病能力越弱。     

群落构建研究的新进展:进化和生态相结合的群落谱系结构研究

群落如何构建足群落生态学中的重要问题.群落谱系结构研究将物种间的亲缘进化关系运用到群落生态学研究中,利用物种的系统发育状况推测历史因素对现有群落的影响,为推断影响群落组成的生态学机制提供了有效方法.群落谱系结构的研究方法是首先建立可代表群落物种库的超级系统进化树,然后计算群落内物种间的谱系距离,最后通过统计方法检测其与随机模型下的谱系距离是否有显著差异来获得谱系结构(如谱系聚集、谱系发散),从而揭示群落构建中的关键生态过程(如生境过滤、竞争作用).群落谱系结构与空间尺度、分类群尺度、时间尺度等不同研究尺度有关.在小的空间尺度下,随着分类群尺度降低、树木年龄级增大,群落谱系结构从聚集逐渐转为发散;而随群落空间尺度的增大,谱系趋向于聚集.谱系结构受到环境因素影响,因此分析集合群落下的谱系可以揭示区域生态过程的影响.另外,群落谱系结构研究还有助于探讨中性理论、密度制约假说等生态学理论,并预测干扰作用下的群落演化趋势.在利用谱系结构深入探讨群落构建成因时,需要基于生态特征和环境变量共同分析,同时考虑小尺度局域过程(群落的微环境或群落内种间相互作用等)和大尺度区域过程(地史过程和物种形成等),并可结合生态控制实验,以确认群落构建的关键因素.在研究方法和手段上,今后需要注重通过选择合适的基因片段建立系统树,然后通过生态特征来加以校正,以更准确地反映物种间的亲缘距离.另外,获得谱系树后还需要寻找更加合理的统计模型和指数,增加统计分析和解决问题的能力.     

Greater than the sum of the parts: how the species composition in different forest strata influence ecosystem function

The mechanisms underpinning forest biodiversity‐ecosystem function relationships remain unresolved. Yet, in heterogeneous forests, ecosystem function of different strata could be associated with traits or evolutionary relationships differently. Here, we integrate phylogenies and traits to evaluate the effects of elevational diversity on above‐ground biomass across forest strata and spatial scales. Community‐weighted means of height and leaf phosphorous concentration and functional diversity in specific leaf area exhibited positive correlations with tree biomass, suggesting that both positive selection effects and complementarity occur. However, high shrub biomass is associated with greater dissimilarity in seed mass and multidimensional trait space, while species richness or phylogenetic diversity is the most important predictor for herbaceous biomass, indicating that species complementarity is especially important for understory function. The strength of diversity‐biomass relationships increases at larger spatial scales. We conclude that strata‐ and scale‐ dependent assessments of community structure and function are needed to fully understand how biodiversity influences ecosystem function.     

Identification of the critical regions in hepatitis B virus preS required for its stability.

As a hepatitis B virus (HBV) envelope domain, preS plays significant roles in receptor recognition and viral infection. However, the regions critical for maintaining a stable and functional conformation of preS are still unclear and require further investigation. In order to unravel these regions, serially truncated fragments of preS were constructed and expressed in Escherichia coli. Their solubility, stability, secondary structure, and affinity to polyclonal antibodies and hepatocytes were examined. The results showed that amino acids 31-36 were vital for its stable conformation, and the absence of 10-36 amino acids significantly reduced its binding to polyclonal antibodies as well as hepatocytes. The most stable fragment 1-120 (preS1 + N-terminal 12 amino acids of preS2), perhaps the core of preS, was discovered, which bound to HepG2 cells most tightly. Moreover, the availability of large amounts of well-folded and stable preS1-120 enables us to carry out further structural determination and mechanistic study on HBV infection.