• 【BAG-1抑制结直肠肿瘤细胞中关键调节细胞因子转化生长因子 β (TGF-β1) 的表达。】 复制标题 收藏 收藏
    DOI:10.1038/onc.2012.480 复制DOI
    作者列表:Skeen VR,Collard TJ,Southern SL,Greenhough A,Hague A,Townsend PA,Paraskeva C,Williams AC
    BACKGROUND & AIMS: :As colorectal cancer remains the second highest cause of cancer-related deaths in much of the industrialised world, identifying novel strategies to prevent colorectal tumour development remains an important challenge. BAG-1 is a multi-functional protein, the expression of which is up-regulated at relatively early stages in colorectal tumorigenesis. Importantly, BAG-1 is thought to enhance colorectal tumour progression through promoting tumour cell survival. Here, we report for the first time a novel role for BAG-1, establishing it as a suppressor of transforming growth factor β (TGF-β1) expression in colorectal tumour cells. Microarray analysis first highlighted the possibility that BAG-1 may regulate TGF-β1 expression, a key cytokine in normal colonic tissue homoeostasis. Q-RT-PCR and ELISA demonstrated TGFB1 mRNA and protein expression to be significantly increased when BAG1 levels were reduced by small interfering RNA; additionally, induction of BAG-1L caused suppression of TGFB1 mRNA in colorectal tumour cells. Using reporter and chromatin immunoprecipitation assays, a direct association of BAG-1 with the TGFB1 gene regulatory region was identified. Immunohistochemistry and Weiser fraction data indicated that the levels of BAG-1 and TGF-β1 are inversely correlated in the normal colonic epithelium in vivo, consistent with a role for BAG-1-mediated repression of TGF-β1 production. In vitro studies showed that the change in TGF-β1 production following manipulation of BAG-1 is functionally relevant; through induction of anchorage-independent growth in TGF-β1-dependent normal rat kidney fibroblasts and regulation of SMAD2 phosphorylation in TGF-β1-sensitive adenoma cells. Taken together, this study identifies the anti-apoptotic protein BAG-1 as a suppressor of the inhibitory growth factor TGF-β1, suggesting that high expression of BAG-1 can impact on a number of the hallmarks of cancer, of potential importance in promoting the early stages of colorectal tumorigenesis. Establishing BAG-1 as a repressor of TGF-β1 has important biological implications, and highlights a new role for BAG-1 in colorectal tumorigenesis.
    背景与目标: : 由于大肠癌仍然是许多工业化国家中癌症相关死亡的第二大原因,因此确定预防大肠癌发展的新策略仍然是一项重要挑战。BAG-1是一种多功能蛋白,其表达在结直肠肿瘤发生的相对早期阶段上调。重要的是,BAG-1被认为可以通过促进肿瘤细胞存活来促进结直肠肿瘤的进展。在这里,我们首次报道了BAG-1的新作用,将其确立为大肠肿瘤细胞中转化生长因子 β (TGF-β1) 表达的抑制因子。微阵列分析首先强调了BAG-1可能调节TGF-β1表达的可能性,TGF-β1是正常结肠组织平衡中的关键细胞因子。Q-rt-pcr和ELISA证明,当小干扰RNA降低BAG1水平时,TGFB1 mRNA和蛋白表达显着增加; 此外,BAG-1L的诱导引起大肠肿瘤细胞中TGFB1 mRNA的抑制。使用报告基因和染色质免疫沉淀测定法,鉴定了BAG-1与TGFB1基因调控区的直接关联。免疫组织化学和Weiser分数数据表明,体内正常结肠上皮中BAG-1和TGF-β1的水平呈负相关,这与BAG-1介导的TGF-β1产生抑制作用一致。体外研究表明,操纵BAG-1后TGF-β1产生的变化在功能上是相关的; 通过诱导TGF-β1依赖性正常大鼠肾脏成纤维细胞中的锚定依赖性生长以及调节TGF-β1敏感性腺瘤细胞中的SMAD2磷酸化。总之,这项研究确定了抗凋亡蛋白BAG-1作为抑制性生长因子TGF-β1的抑制因子,表明BAG-1的高表达可以影响许多癌症的特征,在促进结直肠肿瘤发生的早期阶段具有潜在的重要性。建立BAG-1作为TGF-β1的阻遏物具有重要的生物学意义,并突出了BAG-1在结直肠肿瘤发生中的新作用。
  • 【TGF-β/miR-155/c-Ski调节人冠状动脉内皮细胞间充质转化的机制.】 复制标题 收藏 收藏
    DOI:10.1042/BSR20160603 复制DOI
    作者列表:Wang J,He W,Xu X,Guo L,Zhang Y,Han S,Shen D
    BACKGROUND & AIMS: :Human coronary artery endothelial cells (HCAECs) have the potential to undergo fibrogenic endothelial-mesenchymal transition (EndMT), which results in matrix-producing fibroblasts and thereby contributes to the pathogenesis of cardiac fibrosis. Recently, the profibrotic cytokine transforming growth factor-β (TGF-β) is shown to be the crucial pathogenic driver which has been verified to induce EndMT. C-Ski is an important regulator of TGF-β signaling. However, the detailed role of c-Ski and the molecular mechanisms by which c-Ski affects TGF-β-induced EndMT in HCAECs are not largely elucidated. In the present study, we treated HCAECs with TGF-β of different concentrations to induce EndMT. We found that overexpression of c-Ski in HCAECs either blocked EndMT via hindering Vimentin, Snail, Slug, and Twist expression while enhancing CD31 expression, with or without TGF-β treatment. In contrast, suppression of c-Ski further enhanced EndMT. Currently, miRNA expression disorder has been frequently reported associating with cardiac fibrosis. By using online tools, we regarded miR-155 as a candidate miRNA that could target c-Ski, which was verified using luciferase assays. C-Ski expression was negatively regulated by miR-155. TGF-β-induced EndMT was inhibited by miR-155 silence; the effect of TGF-β on Vimentin, CD31, Snail, Slug, and Twist could be partially restored by miR-155. Altogether, these findings will shed light on the role and mechanism by which miR-155 regulates TGF-β-induced HCAECs EndMT via c-Ski to affect cardiac fibrosis, and miR-155/c-Ski may represent novel biomarkers and therapeutic targets in the treatment of cardiac fibrosis.
    背景与目标: : 人冠状动脉内皮细胞 (HCAECs) 具有发生纤维化的内皮-间质转化 (EndMT) 的潜力,这导致产生基质的成纤维细胞,从而有助于心脏纤维化的发病机理。最近,纤维化细胞因子转化生长因子-β (TGF-β) 被证明是关键的致病驱动因素,已被证实可诱导EndMT。C-ski是TGF-β 信号的重要调节因子。然而,c-Ski的详细作用以及c-Ski影响HCAECs中TGF-β 诱导的EndMT的分子机制尚未得到很大的阐明。在本研究中,我们用不同浓度的TGF-β 处理HCAECs以诱导EndMT。我们发现,有或没有TGF-β 处理,HCAECs中c-Ski的过表达通过阻碍波形蛋白,蜗牛,Slug和Twist的表达来阻断EndMT,同时增强CD31的表达。相比之下,抑制c-ski进一步增强了EndMT。目前,miRNA表达紊乱经常被报道与心脏纤维化有关。通过使用在线工具,我们将miR-155视为可以靶向c-Ski的候选miRNA,使用荧光素酶分析验证了这一点。C-Ski表达受miR-155负调节。TGF-β 诱导的EndMT被miR-155沉默抑制; TGF-β 对波形蛋白,CD31,蜗牛,Slug和Twist的作用可以通过miR-155部分恢复。总之,这些发现将阐明miR-155通过c-Ski调节TGF-β 诱导的HCAECs EndMT以影响心脏纤维化的作用和机制,并且miR-155/c-Ski可能代表治疗心脏纤维化的新型生物标志物和治疗靶标。
  • 【壳聚糖-磷酸甘油/血液植入物增加钻孔软骨缺损中的细胞募集,瞬时血管化和软骨下骨重塑。】 复制标题 收藏 收藏
    DOI:10.1016/j.joca.2006.08.007 复制DOI
    作者列表:Chevrier A,Hoemann CD,Sun J,Buschmann MD
    BACKGROUND & AIMS: OBJECTIVE:Marrow-stimulation techniques are used by surgeons to repair cartilage lesions although consistent regeneration of hyaline cartilage is rare. We have shown previously that autologous blood can be mixed with a polymer solution containing chitosan in a glycerol phosphate (GP) buffer (chitosan-GP), and that implantation of this polymer/blood composite onto marrow-stimulated chondral defects in rabbit and sheep leads to the synthesis of more chondral repair tissue with greater hyaline character compared to marrow-stimulation alone. In the current study, we examined the modulation of cell recruitment and repair tissue characteristics at early post-surgical time points (from day 1 to 56) in a rabbit model to elucidate potential mechanisms behind this improved repair outcome. DESIGN:Thirty-three skeletally mature New Zealand White rabbits underwent bilateral arthrotomies, with each trochlea receiving a cartilage defect (3.5 mm x 4.5mm) bearing four microdrill holes (0.9 mm diameter, approximately 4 mm deep) into the subchondral bone. One defect per rabbit was treated with a chitosan-GP/blood implant, while the other defect was left as a microdrilled control. Repair tissues were stained by histochemistry, for collagen types I, II, and X by immunohistochemistry and analyzed using quantitative stereological tools. RESULTS:Histological analyses demonstrated that control defects followed a typical healing sequence observed previously in marrow-stimulation animal models while chitosan-GP/blood implants led to three significant modifications in the healing sequence at early stages: (1) increased inflammatory and marrow-derived stromal cell recruitment to the microdrill holes, (2) increased vascularization of the provisional repair tissue in the microdrill holes, and (3) increased intramembranous bone formation and subchondral bone remodeling (BR). CONCLUSIONS:These results suggest that the greater levels of provisional tissue vascularization and BR activity are main factors supporting improved cartilage repair when chitosan-GP/blood implants are applied to marrow-stimulated cartilage lesions.
    背景与目标:
  • 【磷酸三甲苯酯诱导的母鸡腰脊髓神经元丢失 -- 免疫组织化学和超微结构研究。】 复制标题 收藏 收藏
    DOI:10.1080/00207450500519655 复制DOI
    作者列表:Mou DL,Wang YP,Song JF,Rao ZR,Duan L,Ju G
    BACKGROUND & AIMS: :To investigate the neuronal losses of hens' spinal cords in the model of organophosphate-induced delayed neuropathy (OPIDN) and to analyze the impact of apoptosis on the pathogenesis of OPIDN. Adult hens were challenged with triorthocresyl phosphate (TOCP) at a single dose (750 mg/kg). Neuronal losses in the 3rd lumbar spinal cord (L3) were assessed by light-microscopy and electron-microscopy methods at different days post exposure, respectively. The typical OPIDN signs were seen in the TOCP-exposed hens at about 9th day. The number of large nerve cells declined gradually. And these cells were verified as neurons by immunostained with neuronal marker NeuN. The expression of FasL reached proximal at about 9th day, decreased from 14th day. Neurons in TOCP exposed groups displayed degenerative morphologies in electronic microscopy. Some neurons showed apoptotic-like ultrastructure profiles at 5th day. The nuclear membrane was complete with chromatin condensed to the margins of nuclear membrane like a crescent-shaped body. Mitochondria morphologic changes appeared early (5 d) following exposure to TOCP, and developed in a time-dependent fashion. Apoptosis might be involved in the development of OPIDN, and play a role in the pathogenesis of OPIDN.
    背景与目标: : 研究有机磷酸盐诱导的迟发性神经病 (OPIDN) 模型中母鸡脊髓的神经元丢失,并分析凋亡对OPIDN发病机理的影响。以单剂量 (750 mg/kg) 对成年母鸡进行磷酸三邻甲苯酯 (TOCP) 攻击。在暴露后的不同天,分别通过光学显微镜和电子显微镜方法评估了第三腰椎脊髓 (L3) 的神经元损失。在大约第9天,在暴露于TOCP的母鸡中可以看到典型的OPIDN迹象。大神经细胞的数量逐渐减少。通过用神经元标记NeuN免疫染色将这些细胞验证为神经元。FasL的表达在第9天左右达到近端,从第14天开始下降。TOCP暴露组的神经元在电子显微镜下显示出退化形态。某些神经元在第5天显示凋亡样超微结构。核膜是完整的,染色质浓缩到核膜的边缘,就像一个新月形的身体。暴露于TOCP后早期 (5 d) 出现线粒体形态变化,并以时间依赖性方式发展。凋亡可能参与OPIDN的发生发展,并在OPIDN的发病机制中起作用。
  • 【放射性碘的雌莫司汀磷酸盐和雌莫司汀结合蛋白抗体在小鼠的前列腺中积累。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0045(19970615)32:1<1::aid-pros1 复制DOI
    作者列表:Ståhlberg K,Kairemo K,Karonen SL,Jekunen A,Taari K,Rannikko S
    BACKGROUND & AIMS: BACKGROUND:The purpose of this study was to determine the distribution of radioiodinated estramustine (RI-EMP) and a radioiodinated antibody against estramustine binding protein (RI-EMBP-AB) in mice. METHODS:RI-EMP and RI-EMBP-AB were injected in male mice intravenously, and the activities of tissue samples were measured 1-31 hr from the injection. Pure iodine-125 (RI) was used as a control. RESULTS:RI-EMP accumulated in the prostate, which contained 2.6% of injected activity (ID) per gram tissue at 7 hr. The liver had an activity of 21.4% ID/g at 1 hr, which decreased as RI-EMP was secreted in bile. The lung contained 2.3% ID/g at 7 hr, and it retained the activity longer than the prostate. RI-EMBP-AB accumulated in the prostate: The activity was 2.9% ID/g at 7 hr. The gallbladder contained 6.5% ID/g at 7 hr. CONCLUSIONS:Due to its cytotoxic and radiosensitizing properties, RI-EMP can possibly be used for treating prostate cancer and other tumors.
    背景与目标:
  • 【由琥珀酸沃林菌分离的ATP合酶催化的磷酸化和磷酸-ATP交换。】 复制标题 收藏 收藏
    DOI:10.1016/0005-2728(85)90218-x 复制DOI
    作者列表:Bokranz M,Mörschel E,Kröger A
    BACKGROUND & AIMS: :The ATP synthase, isolated from Wolinella (formerly Vibrio) succinogenes could be fully incorporated into liposomes without significant cleavage of the enzyme or loss of activity. These proteoliposomes, but not the isolated enzyme, catalyzed phosphate-ATP exchange and the phosphorylation of ADP which was driven by an artificially imposed delta mu H across the liposomal membrane. Phosphorylation driven by light was catalyzed by proteoliposomes containing also bacteriorhodopsin. The three activities were similarly sensitive to protonophores or dicyclohexylcarbodiimide. This sensitivity was similar to that of the electron-transport-driven phosphorylation catalyzed by bacterial membrane vesicles. With a delta mu H value 280 mV to drive phosphorylation the turnover number of the enzyme was in the same order of magnitude as that measured in the electron-transport-driven phosphorylation catalyzed by the bacterial membrane. When the delta mu H was below 150 mV, the phosphorylation activity of the incorporated enzyme was two orders of magnitude slower, and was about as fast as light-driven phosphorylation or as the exchange reaction.
    背景与目标: : 从Wolinella (以前称为弧菌) 琥珀生成素中分离出的ATP合酶可以完全掺入脂质体中,而不会显着裂解酶或丧失活性。这些蛋白脂质体 (而不是分离的酶) 催化了磷酸盐-ATP交换和ADP的磷酸化,而ADP的磷酸化是由在脂质体膜上人工施加的 δ mu H驱动的。光驱动的磷酸化是由也含有细菌视紫红质的蛋白脂质体催化的。这三种活性对原蛋白或二环己基碳二亚胺敏感。这种敏感性与细菌膜囊泡催化的电子传输驱动的磷酸化相似。在280 mV驱动磷酸化的 δ μ H值的情况下,酶的周转数与在由细菌膜催化的电子传输驱动的磷酸化中测量的周转数处于相同的数量级。当 δ μ H低于150 mV时,掺入的酶的磷酸化活性慢两个数量级,并且大约与光驱动磷酸化或交换反应一样快。
  • 【番木瓜脂肪酶在间歇开放反应模式下生物合成 (S)-萘普生淀粉酯。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Wang Y,Xin JY,Li QH,Sun LR,Xia CG
    BACKGROUND & AIMS: :Inorder to brought S-naproxen into small intestine, an optically pure (S)-naproxen starch ester was produced by lipase through enantio-selective trans-esterification of racemic naproxen methyl ester with pretreatment starch in solvent system. With carefully selection of the reaction medium (isooctane), lipase (Carica Papaya Lipase, CPL) and the reaction mode (intermittent opening), a high conversion rate (48.6%) and enantiomeric excess of product (99.6%) was obtained. The slow release macromolecular (S)-Naproxen had been synthesized to improve the efficacy of racemic naproxen and overcome its side effects. The enanitomeric ratio of CPL (E=52.5) was higher than CRL (E=22) and greatly influenced by the byproduct methyl alcohol. The intermittent opening reaction mode was the effective way to remove the inhibition of methyl alcohol and to improve the enantio-selectivity of CPL. S-naproxen starch was confirmed by HPLC and 1H NMR. This method may also apply to preparation the other optically pure 2-phenylpropionic acid derivatives. S-naproxen starch was a new optically pure derivatives possessing emulsifying and slow release properties would be widely applied to the food, pharmaceutical and biomedical industries.
    背景与目标: : 为了将S-萘普生带入小肠,通过脂肪酶通过外消旋萘普生甲酯与预处理淀粉在溶剂体系中的对映选择性酯化反应,制得光学纯的 (S)-萘普生淀粉酯。通过仔细选择反应介质 (异辛烷) 、脂肪酶 (番木瓜脂肪酶,CPL) 和反应模式 (间歇开放),获得高转化率 (48.6%) 和对映体过量的产物 (99.6%)。合成了缓释大分子萘普生,以提高外消旋萘普生的功效并克服其副作用。CPL的烯醇比 (E = 52.5) 高于CRL (E = 22),并且受副产物甲醇的影响很大。间歇开放反应模式是去除甲醇抑制和提高CPL对映体选择性的有效途径。通过HPLC和1H NMR证实了S-萘普生淀粉。该方法也可用于制备其他光学纯的2-苯基丙酸衍生物。S-萘普生淀粉是一种新型的光学纯衍生物,具有乳化和缓释特性,被广泛应用于食品、制药和生物医药行业。
  • 【BEL β-三叶草: 一种在牛肝菌 (牛肝菌) 蘑菇中具有抗肿瘤特性的新型凝集素。】 复制标题 收藏 收藏
    DOI:10.1093/glycob/cws164 复制DOI
    作者列表:Bovi M,Cenci L,Perduca M,Capaldi S,Carrizo ME,Civiero L,Chiarelli LR,Galliano M,Monaco HL
    BACKGROUND & AIMS: :A novel lectin was purified from the fruiting bodies of king bolete mushrooms (Boletus edulis, also called porcino, cep or penny bun). The lectin was structurally characterized i.e its amino acid sequence and three-dimensional structure were determined. The new protein is a homodimer and each protomer folds as β-trefoil domain and therefore we propose the name Boletus edulis lectin (BEL) β-trefoil to distinguish it from the other lectin that has been described in these mushrooms. The lectin has potent anti-proliferative effects on human cancer cells, which confers to it an interesting therapeutic potential as an antineoplastic agent. Several crystal forms of the apoprotein and of complexes with different carbohydrates were studied by X-ray diffraction. The structure of the apoprotein was solved at 1.12 Å resolution. The interaction of the lectin with lactose, galactose, N-acetylgalactosamine and T-antigen disaccharide, Galβ1-3GalNAc, was examined in detail. All the three potential binding sites present in the β-trefoil fold are occupied in at least one crystal form and are described in detail in this paper. No important conformational changes are observed in the lectin when comparing its co-crystals with carbohydrates with those of the ligand-free protein.
    背景与目标: : 从牛肝菌王蘑菇 (牛肝菌,也称为牛肝菌,cep或penny bun) 的子实体中纯化了一种新型凝集素。凝集素的结构表征,即确定其氨基酸序列和三维结构。新蛋白是同型二聚体,每个原聚物都折叠为 β-三叶结构域,因此我们提出了牛肝菌 (Boletus edulis) 凝集素 (BEL) β-三叶,以将其与这些蘑菇中描述的其他凝集素区分开。凝集素对人类癌细胞具有有效的抗增殖作用,这赋予它作为抗肿瘤药的有趣治疗潜力。通过x射线衍射研究了载脂蛋白和与不同碳水化合物的复合物的几种晶体形式。载脂蛋白的结构以1.12的分辨率求解。详细检查了凝集素与乳糖,半乳糖,N-乙酰半乳糖胺和T抗原二糖Galβ1-3GalNAc的相互作用。存在于 β-三叶折叠中的所有三个潜在结合位点均以至少一种晶体形式占据,并在本文中进行了详细描述。将凝集素与碳水化合物的共晶体与无配体蛋白的共晶体进行比较时,未观察到凝集素的重要构象变化。
  • 【靶向脂肪酸酰胺水解酶 (FAAH) 和瞬时受体电位 (TRP) 通道的四氢-β-carboline衍生物。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2012.10.137 复制DOI
    作者列表:Ortar G,De Petrocellis L,Moriello AS,Allarà M,Morera E,Nalli M,Di Marzo V
    BACKGROUND & AIMS: :A series of twenty-five derivatives of tetrahydro-β-carbolines 1-3 was synthesized and assayed on FAAH and TRPV1 and TRPA1 channels. Four carbamates, that is, 5a,c,e, and 9b inhibited FAAH with significant potency and interacted also effectively with TRPV1 and TRPA1 nociceptive receptors, while ureas 7b,d,f, and 8a,b were endowed with specific submicromolar TRPV1 modulating activities.
    背景与目标: : 合成了一系列25种四氢-β-carbolines 1-3衍生物,并在FAAH和TRPV1和TRPA1通道上进行了测定。四种氨基甲酸酯,即5a,c,e和9b以显着的效力抑制FAAH,并且还与TRPV1和TRPA1伤害性受体有效相互作用,而ureas 7b,d,f和8a,b具有特定的亚微摩尔TRPV1调节活性。
  • 【磷酸盐粘合剂治疗对早期慢性肾脏病血管僵硬度的影响。】 复制标题 收藏 收藏
    DOI:10.1159/000353569 复制DOI
    作者列表:Seifert ME,de las Fuentes L,Rothstein M,Dietzen DJ,Bierhals AJ,Cheng SC,Ross W,Windus D,Dávila-Román VG,Hruska KA
    BACKGROUND & AIMS: BACKGROUND/AIMS:Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. METHODS:We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. RESULTS:There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3. CONCLUSION:Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.
    背景与目标:
  • 【蜂胶保护胰岛 β 细胞免受链脲佐菌素 (STZ) 的毒性。】 复制标题 收藏 收藏
    DOI:10.1016/S0944-7113(96)80037-7 复制DOI
    作者列表:Matsushige K,Basnet P,Hase K,Kadota S,Tanaka K,Namba T
    BACKGROUND & AIMS: :Propolis is a glue, prepared by honeybees from plant materials to stick their hives on the beehive wall. It has gained popularity in Japan as a healthy drink and people believe that propolis can cure inflammation, heart diseases and even diabetes and cancer. We have evaluated the β-cell protective effect of propolis against the toxicity of streptozotocin (STZ) in rats. The water extract of propolis (PWE) completely protected β-cell destruction against STZ toxicity. The protective effect of PWE was found to be almost equal to that of nicotinamide. PWE also inhibited the interleukin-1 β (IL-1 β) generation from human leukocytes. The free radical scavenging activity together with IL-1 β and nitric oxide (NO) synthase inhibitory activities are thought to be the prime factors for the protective effect of PWE against STZ toxicity.
    背景与目标: : 蜂胶是一种胶水,由蜜蜂用植物材料制成,将蜂巢粘在蜂巢壁上。它作为一种健康的饮料在日本越来越受欢迎,人们认为蜂胶可以治愈炎症,心脏病,甚至糖尿病和癌症。我们已经评估了蜂胶对大鼠链脲佐菌素 (STZ) 毒性的 β 细胞保护作用。蜂胶 (PWE) 的水提取物完全保护了 β 细胞的破坏免受STZ毒性。发现PWE的保护作用几乎与烟酰胺相同。PWE还抑制人白细胞interleukin-1 β (IL-1 β) 的产生。自由基清除活性以及IL-1 β 和一氧化氮合酶抑制活性被认为是PWE对STZ毒性保护作用的主要因素。
  • 【用玉米淀粉珠通过无污染干磨技术一步制备球形药物颗粒。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2017.06.062 复制DOI
    作者列表:Niwa T,Yoshida M,Hayashi N,Kondo K
    BACKGROUND & AIMS: :The novel dry milling technique has been developed by using a mechanical powder processor for improving the dissolution properties of poorly water-soluble drugs. It was found that the drug crystals were well pulverized by co-processing with fine particles of corn starch (CS). The morphological observation and particle size evaluation revealed that the processed products formed the composite particles with ordered-mixed structure, having double-layered particles with a core of CS and a coating layer of phenytoin (Phe), as a model drug. This result suggested that the drug crystals were selectively micronized and the resultant miniaturized Phe particles were adhered/fixed on the surface of un-milled CS particles. The mechanical characteristics detected by the indentation test assumed that the brittle Phe crystals sandwiched between elastic CS particles would be successfully crushed down by high shearing stress in the processor. The newly-established dispersion-sedimentation test indicated that the fine Phe particles were immediately detached from the composite particles in aqueous phase, constructing the suspension. The dissolution behavior from the processed particles was found to be improved and strongly dependent on the size and amount of detached Phe particles. Such milling and ordered-mixturization have been also successfully done by using recrystallized larger Phe particles than 100μm. These results would propose the contamination-free dry milling technique without using hard milling balls or beads. The mechanism of the current milling and ordered-mixing phenomena is also provided in this report.
    背景与目标: : 通过使用机械粉末处理器开发了新颖的干磨技术,以改善水溶性差的药物的溶解性能。发现通过与玉米淀粉 (CS) 的细颗粒共加工,药物晶体被很好地粉碎。形态观察和粒度评估表明,加工后的产品形成了具有有序混合结构的复合颗粒,具有具有CS核心和苯妥英 (Phe) 涂层的双层颗粒,作为模型药物。该结果表明,药物晶体被选择性微粉化,并且所得的微型Phe颗粒粘附/固定在未研磨的CS颗粒的表面上。通过压痕测试检测到的机械特性假设夹在弹性CS颗粒之间的脆性Phe晶体将被处理器中的高剪切应力成功压碎。新建立的分散沉降测试表明,细小的Phe颗粒立即从水相中的复合颗粒中分离出来,形成了悬浮液。发现处理后的颗粒的溶解行为得到改善,并且在很大程度上取决于分离的Phe颗粒的大小和数量。通过使用重结晶的大于100微米的较大Phe颗粒也成功地完成了这种研磨和有序混合。这些结果将提出无污染的干磨技术,而无需使用硬磨球或珠。本报告还提供了当前铣削和有序混合现象的机理。
  • 【日本一家儿科三级保健医院住院患者直肠携带产超广谱 β-内酰胺酶肠杆菌的比例。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Minami K,Shoji Y,Kasai M,Ogiso Y,Nakamura T,Kawakami Y,Saito Y,Kuzumoto K,Kubota N,Yumoto K,Ishii K
    BACKGROUND & AIMS: :Extended-spectrum β-lactamase (ESBL)-producing-Enterobacteriaceae strains were detected in 12% (6 out of 50) of fecal samples collected from the inpatients of a Japanese pediatric hospital. All the ESBLs belonged to the CTX-M-1 group. The proportion of carriage of ESBL producers was higher among patients who had received antibiotics within the past 3 months and among those who had cardiologic diseases.
    背景与目标: : 在从日本一家儿科医院的住院患者收集的粪便样本中,检测到产生超广谱 β-内酰胺酶 (ESBL) 的肠杆菌科菌株的12% 个 (50个中的6个)。所有的ESBLs都属于CTX-M-1集团。在过去3个月内接受过抗生素治疗的患者和心脏病患者中,ESBL生产者的携带比例较高。
  • 【水凝胶和双相磷酸钙在治疗裂开型种植体周围缺损中的作用: 在狗中的实验研究。】 复制标题 收藏 收藏
    DOI:10.1007/s10856-013-5019-x 复制DOI
    作者列表:Struillou X,Rakic M,Badran Z,Macquigneau L,Colombeix C,Pilet P,Verner C,Gauthier O,Weiss P,Soueidan A
    BACKGROUND & AIMS: :Hydrogel polymers have many applications in regenerative medicine. The aim of this study in dogs was to investigate bone regeneration in dehiscence-type peri-implant defects created surgically and treated with (i) biphasic calcium phosphate (BCP) granules alone; (ii) a composite putty hydroxypropyl methylcellulose (HPMC)/BCP (MBCP/putty); and (iii) a polymer crosslinked membrane of silanized-HPMC (Si-HPMC/BCP) compared with empty controls. At 3 months, new bone formation was significantly more important in defects filled with HPMC/BCP or Si-HPMC/BCP compared with spontaneous healing in control (P = 0.032 and P = 0.046 respectively) and more substantial compared with BCP alone. Furthermore, new bone formation in direct contact with the implant surface was observed in all three groups treated with BCP. The addition of HPMC to the BCP granules may have enhanced the initial stability of the material within the blood clot in these large and complex osseous defects. The Si-HPMC hydrogel may also act as an occlusive membrane covering the BCP, which could improve the stability of the granules in the defect area. However, the crosslinking time of the Si-HPMC is too long for easy handling and the mechanical properties remain to be improved. The composite MBCP/putty appears to be a valuable bone-graft material in complex defects in periodontology and implantology. These encouraging results should now be confirmed in clinical studies.
    背景与目标: : 水凝胶聚合物在再生医学中有许多应用。这项研究的目的是在狗中研究通过手术产生并仅用双相磷酸钙 (BCP) 颗粒治疗的开裂型种植体周围缺损的骨再生; (ii) 复合腻子羟丙基甲基纤维素 (HPMC)/BCP (MBCP/putty); (iii) 与空对照相比,硅烷化-HPMC (Si-HPMC/BCP) 的聚合物交联膜。在3个月时,与对照组的自发愈合相比,新骨形成在HPMC/BCP或Si-HPMC/BCP填充的缺损中明显更重要 (分别为P = 0.032和P = 0.046),并且与单独的BCP相比更重要。此外,在接受BCP治疗的所有三组中,均观察到与植入物表面直接接触的新骨形成。在BCP颗粒中添加HPMC可能会增强这些大而复杂的骨缺损中血凝块内材料的初始稳定性。Si-HPMC水凝胶也可以充当覆盖BCP的闭塞膜,这可以改善缺陷区域中颗粒的稳定性。然而,Si-HPMC的交联时间太长,无法轻松处理,并且机械性能仍有待改善。在牙周病学和种植学的复杂缺陷中,复合MBCP/腻子似乎是一种有价值的骨移植材料。这些令人鼓舞的结果现在应该在临床研究中得到证实。
  • 【在化妆品配方中装有精油的壳聚糖珠。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Anchisi C,Meloni MC,Maccioni AM
    BACKGROUND & AIMS: :The aim of this work is to evaluate the stability and release of chitosan beads loaded with volatile molecules of Mentha piperita essential oil (E.O.) in a cosmetic formulation. The ability of the beads to quickly release Mentha piperita E.O. during use of a cosmetic formulation such as a bath foam is also assessed. The chitosan beads were produced with three different chitosan dispersions gelled with two different gelling solutions: (a) a 10% solution of sodium hydroxide (NaOH) and (b) a 4% solution of sodium tripolyphosphate (TPP). A few properties of six bead samples loaded with Mentha piperita E.O. are assessed. The properties are morphology, size, swelling ability, encapsulation efficiency, stability in time, and fast release of Mentha piperita E.O. during the use phase of the cosmetic formulation.
    背景与目标: : 这项工作的目的是评估在化妆品配方中负载有薄荷糖精油 (E.O.) 挥发性分子的壳聚糖珠的稳定性和释放。还评估了在使用化妆品配方 (例如浴泡沫) 期间,珠子快速释放薄荷的能力。用三种不同的壳聚糖分散体用两种不同的胶凝溶液 (a) 氢氧化钠 (NaOH) 的10% 溶液和 (b) 三聚磷酸钠 (TPP) 的4% 溶液制备壳聚糖珠。六个装有Mentha piperita e.o的珠子样品的一些特性。评估。性质是形态,大小,溶胀能力,包封效率,在时间上的稳定性,以及在化妆品配方的使用阶段的薄荷的快速释放。

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