(2-Hydroxypropyl)-β-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis

BackgroundPeripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that β-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-β-cyclodextrin (2HP-β-CD).ConclusionsTherapeutic angiogenesis by 2HP-β-CD may be beneficial to patients with PAD.     

The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells

Activated pancreatic stellate cells (PaSC) are key participants in the stroma of pancreatic cancer, secreting extracellular matrix proteins and inflammatory mediators. Tumors are poorly vascularized, creating metabolic stress conditions in cancer and stromal cells that necessitate adaptive homeostatic cellular programs. Activation of autophagy and the endoplasmic reticulum unfolded protein response (UPR) have been described in hepatic stellate cells, but the role of these processes in PaSC responses to metabolic stress is unknown. We reported that the PI3K/mTOR pathway, which AMPK can regulate through multiple inputs, modulates PaSC activation and fibrogenic potential. Here, using primary and immortalized mouse PaSC, we assess the relative contributions of AMPK/mTOR signaling, autophagy and the UPR to cell fate responses during metabolic stress induced by mitochondrial dysfunction. The mitochondrial uncoupler rottlerin at low doses (0.5–2.5 μM) was added to cells cultured in 10% FBS complete media. Mitochondria rapidly depolarized, followed by altered mitochondrial dynamics and decreased cellular ATP levels. This mitochondrial dysfunction elicited rapid, sustained AMPK activation, mTOR pathway inhibition, and blockade of autophagic flux. Rottlerin treatment also induced rapid, sustained PERK/CHOP UPR signaling. Subsequently, high doses (>5 μM) induced loss of cell viability and cell death. Interestingly, AMPK knock-down using siRNA did not prevent rottlerin-induced mTOR inhibition, autophagy, or CHOP upregulation, suggesting that AMPK is dispensable for these responses. Moreover, CHOP genetic deletion, but not AMPK knock-down, prevented rottlerin-induced apoptosis and supported cell survival, suggesting that UPR signaling is a major modulator of cell fate in PaSC during metabolic stress. Further, short-term rottlerin treatment reduced both PaSC fibrogenic potential and IL-6 mRNA expression. In contrast, expression levels of the angiogenic factors HGF and VEGFα were unaffected, and the immune modulator IL-4 was markedly upregulated. These data imply that metabolic stress-induced PaSC reprogramming differentially modulates neighboring cells in the tumor microenvironment.     

Gap pattern and colonization opportunities in plant communities: effects of species richness, mortality, and spatial aggregation

We investigate how perturbations that induce mortality transform original spatial patterns in plant communities into binary spatial patterns of survivors and perished individuals. By means of computer simulation, we analyse effects of average mortality, interspecific variation of mortality around the mean, spatial distribution of the species (clumping degree), and species richness. Gap spatial pattern is quantified by four spatial indices or landscape metrics (gap area, density, shape and coherence). In single‐species communities, the emerging gap patterns are subject to critical phenomena: opportunities for colonizers to establish increase with mortality, but more rapidly at specific mortality thresholds. In multi‐species communities, neither species richness nor interspecific variation of mortality influences gap spatial pattern when community assembly is random. Colonization opportunities would therefore not be affected by local species extinction in such a system, nor by the presence of species with divergent sensitivities to perturbation. In a community that is highly spatially aggregated, increases in interspecific mortality variation shift the pattern towards fewer gaps that are larger and more isodiametric, which suggests increased establishment chances for colonizers. Similar changes are induced in communities characterized by large interspecific mortality differences if clumping degree is increased. Loss of species richness only modifies gap spatial pattern to a substantial extent if mortality variation is high: in this case, depauperate communities exhibit a wider variety of colonization opportunities (more gaps which are on average smaller, but the largest gap is larger) than species‐richer ones. These findings may explain the contrast between the negative diversity‐invasibility relationship often found in small‐scale experimental studies and the positive diversity‐invasibility relationship found in observational studies at larger scale. They also demonstrate that the pre‐disturbance spatial structure of a community significantly affects colonization opportunities for alien species, and is therefore a likely determinant of the trajectory of secondary succession following perturbation.     

东方田鼠种群扩散及活动对外部因子的反应格局

在野外围栏条件下,采用2×2×2析因实验,测定外部因子食物、捕食,以及同域分布物种黑线姬鼠的种间竞争对东方田鼠扩散和活动距离的独立作用及其交互作用的效应。研究结果表明,在所有的扩散个体中,幼体扩散的比例为71.0%。雄体扩散的比例为80.5%。东方田鼠扩散的趋势与其种群密度及补充量的变动一致。食物对扩散具有显著独立作用;捕食对扩散的作用接近显著;种间竞争对扩散的直接效应不显著;食物、捕食与种间竞争交互作用对扩散的效应亦不显著。在诱捕期内雄性的长距离活动比例及其诱捕期间长距离活动比例均显著大于诱捕期内雌性及其诱捕期间的长距离活动比例。不同处理种群间,仅雄体在诱捕期间的长距离活动比例具有显著差异;食物对雄体的长距离活动具有直接和间接(通过密度)的效应;而预防捕食者和竞争物种对不同处理种群雄体的长距离活动则无一致的效应。     

以重组TACE胞外功能域从噬菌体随机肽库中筛选TACE的抑制肽

肿瘤坏死因子转换酶 (TACE)是加工裂解TNF-α前体的关键酶 ,参与了许多炎症的发生发展过程。为通过肽库筛选得到TACE的抑制肽 ,首先制备筛选靶分子 ,用RT PCR从人外周血单核细胞中分别扩增出TACE的催化区 (T800 )和整个胞外区 (T1300 ) ,然后分别克隆至pET-28a和pET-28c中 ,转化大肠杆菌BL2-1(DE3) ,经IPTG诱导表达出带有His-tag的目的蛋白 ,两者均为包涵体 ,变性复性后过Ni²⁺-NTA亲和层析柱得到纯度达90%的重组蛋白。以纯化的重组T800和T1300分别筛选噬菌体展示随机 15肽库 ,对筛选克隆进行ELISA检测、竞争抑制实验和序列分析。从两个独立的筛选过程中得到一个相同的阳性克隆序列“TRWLVYFSRPYLVAT” ,固相Fmoc法合成该短肽 ,观察其在LPS诱导人单核细胞产生sTNF-α中的作用。结果表明 ,筛选到的短肽可显著抑制TACE的活性 ,减少TNF-α的分泌 ,抑制率可达 60.3% ,为抗炎小分子药物的设计和改造提供线索和依据。     

酵母菌中谷胱甘肽的主要生理功能及其代谢调控

谷胱甘肽是生物体内一种重要的三肽小分子 ,具有广泛的生理功能。对谷胱甘肽在酵母细胞中的作用及其代谢调控机制 ,做了较为详细的介绍。这一带有基础性研究的内容 ,对于以酵母为生产菌的谷胱甘肽的生产 ,或是酵母的其他工业化生产 ,具有重要的启示。     

新疆苦豆子根瘤菌的数值分类研究

苦豆子(Sophora alopecuroides)对于干旱荒漠地区的畜牧业发展有着非常重要的意义,其生长特性与根瘤菌有密切关系。我们对分离自新疆苦豆子根瘤的67株根瘤菌及36个模式菌株进行了118项表型性状的测定,包括唯一碳源利用、唯一氮源利用、对抗生素和染料的抗性、耐盐性、初始pH值生长范围、生长温度范围及石蕊牛奶反应、氧化酶、过氧化氢酶和脲酶。对测定结果用聚类分析方法进行了分析,获得数值分类树状图。结果表明：新疆苦豆子根瘤菌在碳氮源利用、抗生素敏感性以及对染料的抗性程度等方面存在着差异。新疆苦豆子根瘤菌能耐受低温,并具有较强的耐盐、碱能力,所有供试菌株均能在初始pH值为9－12的YMA培养基上生长,92.5％的菌株能耐受3.0％的NaCl,91.0％的菌株能耐受4.0％的NaCl,有18株菌甚至能耐受5.0％和6.0％的NaCl。聚类结果表明, 在84.8%的相似性水平上,67个供试菌株构成了4个新的表观群,第Ⅰ、Ⅱ、Ⅲ、Ⅳ类群分别有21、7、4、3个菌株,中心菌株分别为NWBC152、NWTKX101、NWYJS12、NWLP112。此外,数值分类结果还表明,苦豆子根瘤菌与模式菌株的相似性较低,它们所形成的4个独立群可能有新种出现。     

滇牡丹遗传多样性的ISSR分析

应用ISSR标记对中国西南地区特有植物滇牡丹(Paeonia delavayi)的遗传多样性进行了研究。从100个引物中筛选出10个用于正式扩增,在取自16个自然居群和1个迁地保护居群的511个个体中,检测到92个多态位点。在居群水平上,多态位点百分率（PPB）为44.61%,Nei′s基因多样性指数（H）和Shannon信息指数（I）分别为0.1657和0.2448。在物种水平上,多态位点百分率（PPB）为79.31%,Nei′s基因多样性指数（H）和Shannon信息指数（I）分别为0.2947和0.4355。居群间的遗传分化系数(G_ST)达0.4349。结果表明：滇牡丹遗传多样性水平较高,居群间遗传分化较大。结合以前的研究结果,对滇牡丹的现状进行评估的结果显示,滇牡丹并不濒危。