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81.
Doxorubicin (Dox), one of the most used chemotherapeutic agents, is known to generate oxidative stress and block DNA synthesis, which result in severe dose-limiting toxicity. A strategy to protect against Dox toxic effects could be to use dietary antioxidants of which fruits and vegetable are a rich source. In this context, strawberry consumption is associated with the maintenance of good health and the prevention of several diseases, thanks to the antioxidant capacities of its bioactive compounds. The aim of the present study was to evaluate the protective effects of strawberry consumption against oxidative stress induced by Dox in rats. Animals were fed with strawberry enriched diet (15% of the total calories) for two months and Dox (10 mg/kg; i.p.) was injected at the end of the experimental period. Strawberry consumption significantly inhibited ROS production and oxidative damage biomarkers accumulation in plasma and liver tissue and alleviated histopathological changes in rat livers treated with Dox. The reduction of antioxidant enzyme activities was significantly mitigated after strawberry consumption. In addition, strawberry enriched diet ameliorated liver mitochondrial antioxidant levels and functionality. In conclusion, strawberry intake protects against Dox-induced toxicity, at plasma, liver and mitochondrial levels thanks to its high contents of bioactive compounds. 相似文献
82.
Elhadj S. Baldé Véronique Megalizzi Mohamed S. Traoré Paul Cos Louis Maes Christine Decaestecker Luc Pieters Aliou M. Baldé 《Journal of ethnopharmacology》2010
Aim of the study
To study the potential benefit of the traditional medicinal plant Pavetta crassipes K. Schum (Rubiaceae), which is widely distributed throughout West Africa, the methanol and dichloromethane extracts were isolated from the plant leaves to determine if they exhibited antiprotozoal, antibacterial, antifungal or antitumor activity in vitro.Materials and methods
The methanol and dichloromethane extracts and their specific fractions were obtained using bioassay-guided fractionation and investigated for antiproliferative activity in vitro in microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans), protozoans (Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum and Plasmodium falciparum), and cancer (U373, PC3, MXT and A549) and normal cell lines (NHDF and MRC-5).Results
Most of the alkaloid fractions investigated exhibited antiproliferative activity in all the cancer cell lines, microorganisms and protozoans studied.Conclusions
The benefit of Pavetta crassipes as a traditional medicinal remedy was confirmed using antiprotozoal and cytotoxicity assays in vitro. These analyses revealed that the components present in the alkaloid extract of Pavetta crassipes are responsible for its antiprotozoal and cytotoxic efficacy. 相似文献83.
Case studies covering carbonaceous nanomaterials, metal oxide and metal sulphate nanomaterials, amorphous silica and organic pigments were performed to assess the Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping). The usefulness of the DF4nanoGrouping for nanomaterial hazard assessment was confirmed. In two tiers that rely exclusively on non-animal test methods followed by a third tier, if necessary, in which data from rat short-term inhalation studies are evaluated, nanomaterials are assigned to one of four main groups (MGs). The DF4nanoGrouping proved efficient in sorting out nanomaterials that could undergo hazard assessment without further testing. These are soluble nanomaterials (MG1) whose further hazard assessment should rely on read-across to the dissolved materials, high aspect-ratio nanomaterials (MG2) which could be assessed according to their potential fibre toxicity and passive nanomaterials (MG3) that only elicit effects under pulmonary overload conditions. Thereby, the DF4nanoGrouping allows identifying active nanomaterials (MG4) that merit in-depth investigations, and it provides a solid rationale for their sub-grouping to specify the further information needs. Finally, the evaluated case study materials may be used as source nanomaterials in future read-across applications. Overall, the DF4nanoGrouping is a hazard assessment strategy that strictly uses animals as a last resort. 相似文献
84.
目的探讨利用脉冲激光沉积(PLD)方法在人工心脏机械瓣膜上沉积的纳米相羟基磷灰石(HA)薄膜的组织相容性,为人工心脏瓣膜的构建提供理想的支架薄膜材料。方法将传代的人血管内皮细胞制成细胞悬液接种在HA材料上,置含5%(V/V)CO2、37℃的恒温培养箱内静态培养3周。分别在培养3、7、14和21d后取出部分材料,用2.5%戊二醛固定,乙醇梯度脱水,临界点干燥、喷金,于扫描电子显微镜(SEM)下观察细胞在材料上的附着情况。用四氮唑盐比色(MTT)法测定血管内皮细胞与材料复合培养的增殖能力。结果扫描电镜观察复合培养,见HA材料的表面有细胞附着且数目逐渐增多,到第21天时可见细胞融合成片,并将材料表面覆盖,部分区域有细胞外基质形成。MTT法评价材料对血管内皮细胞的细胞毒性,见细胞增殖未受到明显影响,生长良好。结论HA对血管内皮细胞的增殖和分化功能无明显影响,对细胞无明显毒性,具有良好的生物相容性,可以作为心脏瓣膜材料安全应用。 相似文献
85.
目的和方法:选用正常大鼠肺泡巨噬细胞(AM),在高糖及高糖+高胰岛素环境下培养,用卡介苗(BCG)、干扰素α-2b(IFNα-2b)或两者联合活化,检测其贴壁率、四唑氮兰(NBT)还原功能、NO和TNF-α释放量并观察其超微结构改变。结果:高糖及高糖+高胰岛素环境下活化AM贴壁延迟(P<0.01),NBT还原功能明显被抑制(P<0.01);BCG和IFNα-2b+BCG活化AM时,其NO和TNFα释放量均明显低于对照组(P<0.01);IFNα-2b活化AM时,其NO和TNF-α释放量与对照组无明显差别(P>0.05);细胞表面伪足减少、变短,胞质内高尔基氏体、粗面内质网减少。结论:在短期内高糖及高糖+高胰岛素环境均抑制AM吞噬功能及改变超微结构,从而使糖尿病个体易发生肺部感染。 相似文献
86.
Gil Chernin Iris Szwarcfiter Yvonne Bausback Michael Jonas 《Journal of vascular and interventional radiology : JVIR》2017,28(5):740-748
Purpose
To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter–based renal sympathetic denervation (RDN) system in normotensive swine.Materials and Methods
RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries).Results
In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent.Conclusions
The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries. 相似文献87.
88.
Hirata H Hinoda Y Majid S Chen Y Zaman MS Ueno K Nakajima K Tabatabai ZL Ishii N Dahiya R 《Cancer》2011,117(8):1649-1660
BACKGROUND:
To the authors' knowledge, the functional significance of the Wnt antagonist dickkopf homolog 4 (DKK4) has not been investigated previously in renal cancer.METHODS:
The authors initially observed that the expression of DKK4 was significantly higher in renal cancer tissues compared with adjacent normal kidney tissues. To assess the function of DKK4, stable DKK4‐transfected cells were established, and functional analyses were performed, including a T‐cell factor/lymphoid enhancer factor (TCF/LEF) reporter assay and tests for cell viability, colony formation, apoptosis, cell cycle, invasive capability, wound‐healing capability, and in vivo tumor growth.RESULTS:
The relative TCF/LEF activity was significantly lower in DKK4‐transfected cells compared with empty vector, and nuclear β‐catenin expression was decreased in DKK4 transfectants. In addition, expression levels of the β‐catenin downstream effector proteins cyclin D1 and c‐Myc were decreased in DKK4 transfectants. However, greater invasiveness and migration were observed in stably transfected DKK4 cells. Increased growth of DKK4‐transfected tumors also was observed in nude mice. Members of the Wnt noncanonical/c‐Jun‐NH2 kinase (JNK) signaling pathway also were effected, such as c‐Jun, which had significantly increased expression and phosphorylation in DKK4‐stable transfectants, and matrix metalloproteinase‐2, which had significantly increased expression in DKK4‐stable transfectants.CONCLUSIONS:
This is the first study to indicate that DKK4 expression is increased in renal cancer tissues and that DKK4 activates the noncanonical JNK signaling pathway while inhibiting the Wnt‐canonical pathway. Cancer 2011. © 2010 American Cancer Society. 相似文献89.
Nuclear factor-kappaB (NF-κB) is constitutively activated in a variety of human cancers including prostate cancer and involved in tumorigenesis, tumor progression and chemo-resistance. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a potent tumor suppressor and is significantly suppressed in a variety of cancers. Diverse biological effects of IGFBP-3 have been reported to be both dependent and independent of the IGF/IGF-I receptor (IGF-IR) axis. The precise underlying mechanisms of IGF/IGF-IR-independent, antiproliferative actions of IGFBP-3 are yet to be elucidated. We found an inverse correlation between NF-κB activity and IGFBP-3 expression during prostate cancer progression using an in vitro prostate cancer progression model. Restoration of IGFBP-3 resulted in significant inhibition of constitutively elevated NF-κB activity in prostate cancer cells. IGFBP-3 further inhibited the expression of NF-κB-regulated angiogenic factors such as VEGF and IL-8, and cell adhesion molecules, ICAM-1 and VCAM-1. This inhibitory action of IGFBP-3 was IGF/IGF-IR-independent since IGFBP-3 mutant devoid of IGF binding affinity had a similar inhibitory effect. We identified that IGFBP-3 degrades the key NF-κB regulatory molecules-IκBα and p65-NF-κB proteins through activation of caspase-8 and -3/-7, thereby inhibiting elevated NF-κB activity in prostate cancer. Finally intratumoral administration of IGFBP-3 resulted in significant tumor suppression as well as sensitization of antitumor effect of doxorubicin. Our findings indicate that IGFBP-3 exerts antitumor effects via IGF-independent mechanisms which involve activation of caspase-dependent apoptosis and cross-talk with NF-κB signaling. The use of IGFBP-3 as a cancer therapeutic with this distinctive suppression mechanism may offer alternate means to treat chemotherapy resistant tumors. 相似文献
90.
目的 探讨轴索型腓骨肌萎缩症2L(axonal Charcot-Marie-Tooth disease type 2L,CMT2L)K141N突变的热休克蛋白B8(heat shock protein B8,HSPB8)对细胞相对活力的影响.方法 应用脂质体转染技术,将野生型HSPB8(wt HSPB8)和K141N突变型HSPB8( K141N HSPB8)分别转染SHSY-5Y细胞,使其过量表达上述蛋白,以表达绿色荧光蛋白(green fluorescent protein,GFP)为阴性对照,转染24 h后用44℃致死性热休克处理40 min,用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)比色法检测SHSY-5Y细胞的相对活力.结果 未处理组pEGFP-wt HSPB8与pEGFP-K141N HSPB8组间吸光度值比较P>0.05,而热休克处理组pEGFP-wt HSPB8与pEGFP-K141N HSPB8组间吸光度值比较P<0.05,表明热休克处理后各组细胞相对活力差异有统计学意义,热休克处理后过表达wt HSPB8的SHSY-5Y细胞活力最高,过表达K141N HSPB8的细胞次之,过表达GFP空载体的细胞活力最低.结论 证实了HSPB8在细胞受到致死性热休克刺激时对于保护细胞活力方面起着重要作用,K141N突变型HSPB8对细胞相对活力的保护作用较野生型HSPB8减弱. 相似文献