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Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis.  相似文献   
13.
The whitefly Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) is a species complex, and its systematic classification requires controlled crossing experiments among its genetic groups. Accurate information on pre‐copulation intervals, copulation frequencies, and initial frequency of egg fertilization of newly emerged adults is critical for designing procedures for collecting the virgin adults necessary for these experiments. In the literature, considerable variation is reported between B. tabaci populations, with respect to the length of the pre‐copulation interval and the initial frequency of egg fertilization. Here, we used a video‐recording method to observe continuously the copulation behaviour of the Mediterranean/Asia Minor/Africa (B biotype) and the Asia II (ZHJ1 biotype) groups of B. tabaci. We also recorded the initial frequency of egg fertilization, as determined by the sex of the progeny. When adults were caged in female–male pairs on leaves of cotton plants, the earliest copulation events occurred 2–6 h after emergence; at 12 h after emergence 56–84% of the females had copulated at least once, and nearly all (92–100%) had copulated at least once by 36 h after emergence. Both females and males copulated repeatedly. Approximately 80 and 20% of copulation events occurred during the photophase and scotophase, respectively. By 72 h post‐emergence, the females of the B and ZHJ1 biotypes had copulated on average 6.1 and 3.9 times, respectively. When adults were caged in groups on plants 1–13 h after emergence, 30–35% of the eggs deposited during this period were fertilized, and approximately 90% of females were fertilized by the end of the 13 h. Although timing of copulation differed in detail between the two genetic groups, the results demonstrate that B. tabaci adults can start to copulate as early as 2–6 h post‐emergence and the majority of females can become fertilized on the day that they emerge.  相似文献   
14.
Nodal cuttings of white yam were induced to produce microtubers on a MS-revised medium supplemented with various concentrations of sucrose, 20 mgl–1 L-cysteine, 0.5 mgl–1 kinetin and 0.7% agar. The frequency of tuberization was affected by the daylength, which is optimal at 12 and 16 h of light depending on the sucrose concentration. The microtubers were planted in a seed bed and grown to maturity. The importance of in vitro tuberization of yam as a means of international germplasm distribution or exchange as well as for the propagation of planting material is discussed.  相似文献   
15.
The present prospective study showed that incidence of systemic infection in severe burn patients was 30.9%. Toxic shock and multiple organ failure (MOF) developed in all patients with uncontrolled systemic infection. Both morbidity and mortality of MOF were 76.5%. In the infection group, plasma TXB(2) and TXB(2)/6-keto-PGF(1alpha) ratio increased markedly. Their changes were closely correlated with the clinical course and deterioration of systemic infection. Circulatory platelet aggregate ratio decreased significantly, while myocardiac enzyme spectrum greatly increased. Thrombi were observed in visceral tissues from patients dying of systemic infection. These suggested that TXA(2)/PGI(2). imbalance promoting microaggregate and thrombus formation may be one of the pathogenic effects of toxic shock and MOF in burn patients.  相似文献   
16.

1. 1.|When Chinese hamster ovary cells are treated with cycloheximide (10 μg/ml) or puromycin (100 μg/ml) for 2 h before and during heating at 43°C for 3 h, there is protection from hyperthermic killing; i.e. the plating efficiency increases 2000-fold from 3.7 × 10−5 to (6–9) × 10−2.

2. 2.|The total intracellular levels of spermidine and spermine are not altered by the hyperthermic or drug treatments.

3. 3.|The small 30% decrease in intracellular putrescine observed after heating is not altered by drug treatment.

4. 4.|Heat protection by treatment with cycloheximide or puromycin cannot be attributed to changes in levels of total intracellular polyamines.

Author Keywords: Heat protection; cycloheximide; puromycin; putrescine; spermidine; spermine  相似文献   

17.
长非编码RNA(long non-coding RNAs, lncRNAs)在肿瘤发生、发展进程中承担重要角色,是近年来的研究热点之一。大量研究表明,浆细胞瘤变异易位基因1(plasmacytoma variant translocation 1, PVT1)可通过多种分子机制参与调控消化系统肿瘤的增殖凋亡、迁移侵袭、细胞自噬、血管生成、多药耐药及肿瘤代谢等过程,从而发挥致癌作用。本文主要就PVT1在消化系统肿瘤中的表达水平变化,及其与临床病理特征和预后的关系,以及PVT1对消化系统肿瘤的致癌作用机制和多药耐药机制等研究进展作一综述。  相似文献   
18.
ELECTRON MICROSCOPY OF VIRUS-INFECTED YEAST CELLS   总被引:1,自引:0,他引:1  
  相似文献   
19.
本文报告了25%烧伤后注射免疫抑制剂(地寨米松磷酸钠)大鼠7种肠道细菌的定量、内脏及血液的细菌培养和肠壁的病理形态学改变。单纯烧伤组(B组)和单纯注射免疫抑制剂组(Ⅰ组)动物肠壁的病理改变较轻,肠道菌群改变不明显,其肠道细菌易位率也很低。烧伤后注射免疫抑制剂的动物(BⅠ组)肠壁病变严重,肠道菌群改变明显。其中,肠杆菌在回肠、盲肠,结肠内容物中的菌量均明显升高;回肠内容物中拟杆菌的菌量明显减少;该组动物肠道细菌易位率也明显增高,达60%。此外,BⅠ组、Ⅰ组部分动物发生了由棒状杆菌及由棒状扦菌和肠杆菌混合引起的内源性感染。根据不同肠段肠壁病变严重程度、菌群变化的部位以及不同部位肠管生理功能的不同,我们推测,回肠以上肠段是肠道细菌易位的主要部位。  相似文献   
20.
可育的抗除草剂溴苯腈转基因小麦   总被引:21,自引:0,他引:21  
报道了采用微粒轰击(Microprojectile bom bardm ent) 幼胚将除草剂抗性基因导入小麦(Triticumaestivum L.)的转化研究。实验共使用了13 个小麦品种, 从开花后14~18 d 的籽粒中剥取幼胚, 植物表达质粒含有CaMV 35S启动子控制的除草剂溴苯腈抗性基因bxn 以及筛选标记基因NTPⅡ。采用高压放电基因枪,用质粒DNA 包被的钨粒轰击预培养3 d 的幼胚。在含有卡那霉素类似物geneticin G418sulphate 的MS培养基上, 经过多步骤筛选和分化, 从800 多个幼胚中获得了16 株转化苗。除草剂抗性鉴定和Southern 杂交分析证明, 其中4 株为转基因植物,具有溴苯腈抗性, 并且自交可育。转化工作从分离幼胚到转化苗鉴定完毕, 最短时间为6 个月, 因此, 该方法是一项快速有效的基因导入技术  相似文献   
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