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191.
Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels 总被引:8,自引:0,他引:8
Hassani Z Lemkine GF Erbacher P Palmier K Alfama G Giovannangeli C Behr JP Demeneix BA 《The journal of gene medicine》2005,7(2):198-207
BACKGROUND: Efficient in vivo vectors are needed to exploit the enormous potential of RNA interference (RNAi). Such methods require optimisation for specific delivery routes, tissues and usages. We tested the capacity of different non-viral vectors and formulation methods for inhibition of exogenous (luciferase) gene expression when used to introduce small interfering RNA (siRNA) into the mouse brain in vivo. METHODS: Polyethylenimine (PEI)-based polyplexes and JetSI (a mixture of cationic lipids)-based lipoplexes were used to vectorise plasmid DNA encoding the firefly Photinus pyralis luciferase gene and picomolar amounts of siRNA directed against this gene. Two controls were used, DNA encoding an unrelated luciferase from Renilla reniformis and a mutated siRNA sequence. RESULTS: First, we found that linear PEI, although efficient for delivering nucleic acids to cells, did not permit development of siRNA activity within the dose range tested (<0.5 pmol). Second, various combinations of cationic lipids were tried and the best formulation was found to be a combination of JetSI with the fusogenic lipid dioleoylphosphatidylethanolamine (DOPE). Efficient inhibition of target, firefly luciferase was obtained with exceedingly low amounts of siRNA: 78 +/- 6% inhibition at 24 h post-transfection with 0.2 pmol siRNA. This inhibition was dose-dependent and specific. No effect was seen on the control gene, co-transfected Renilla luciferase, and the control mutated siRNA sequence had no effect on the targeted firefly luciferase. CONCLUSIONS: We have optimised an efficient cationic lipoplex method for delivery of siRNA into the newborn mouse brain. Specific inhibition of exogenous target gene expression is obtained with picomolar amounts of siRNA. 相似文献
192.
Tiatou Souho Hinde El Fatemi Safae Karim Karima El Rhazi Chahrazed Bouchikhi Abdelaziz Banani Moulay Abdelilah Melhouf Mohamed Benlemlih Bahia Bennani 《PloS one》2016,11(1)
Objectives
To determine the distribution of cervical high-risk human papillomavirus genotypes and their association to cellular abnormalities in women from Fez and its neighborhood.Methods
Women attending the Hassan II University Hospital for cervical pap smears were recruited after an informed consent. Interviews and two cervical samples were performed for each woman. Cervical samples were used for cytological analysis and HPV DNA detection. HPV was typed using a method based on multiplex PCR with fluorescently labeled specific primers followed by capillary electrophoresis. The study was approved by the ethics committee of the Faculty of Medicine and Pharmacy of Fez.Results
The HPV prevalence in the studied population was 43.1% and the most prevalent types were HPV 53 (23 cases); HPV 16 (20 cases); HPV 35 (18 cases); HPV 51 (10 cases) and HPV 56 (7 cases). From the 619 confirmed pap smears, 20% were abnormal. The cytological abnormalities were significantly associated to HPV infection, women age, number of pregnancies and parity (p < 0.05).Conclusion
More attention should be given to HPV in Morocco because it represents an important public health concern. The distribution of carcinogenic HPV types in the studied population is different from the data in other regions but epidemiological studies in other Moroccan regions are required. 相似文献193.
Karima Begriche Julie Massart Adjé Abbey‐Toby Anissa Igoudjil Philippe Lettéron Bernard Fromenty 《Obesity (Silver Spring, Md.)》2008,16(9):2053-2067
β‐Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild‐type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high‐calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma β‐hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase‐1 was augmented in liver and white adipose tissue. Acetyl‐CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin‐dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet‐induced obesity and related metabolic disorders in low leptin secretors. 相似文献
194.
Les insectes butineurs de Cucumis sativus L. (Cucurbitaceae) ont été étudiés durant les floraisons de 2001 et de 2002 dans la région de Constantine (est algérien). Les observations ont montré que la majorité des visiteurs de la plante sont des hyménoptères apoïdes. Apis mellifera L., Ceratina cucurbitina Rossi, Megachile leachella Curtis et M. pilidens Alfken sont les espèces les plus fréquentes sur les fleurs. Les proportions de visites des abeilles sont plus élevées sur les fleurs staminées que sur les fleurs pistilées. En moyenne, les quatre espèces ont visité entre 6 et 8 fleurs par minute et leurs durées de visite sur les fleurs pistilées sont significativement plus lentes en comparaison avec les fleurs staminées. 相似文献
195.
Mutations that affect the tropism of DA and GDVII strains of Theiler's virus in vitro influence sialic acid binding and pathogenicity 下载免费PDF全文
Theiler's murine encephalomyelitis virus (TMEV) is a natural pathogen of the mouse. The different strains of TMEV are divided into two subgroups according to the pathology they provoke. The neurovirulent strains GDVII and FA induce an acute fatal encephalitis, while persistent strains, like DA and BeAn, cause a chronic demyelinating disease associated with viral persistence in the central nervous system. Different receptor usage was proposed to account for most of the phenotype difference between neurovirulent and persistent strains. Persistent but not neurovirulent strains were shown to bind sialic acid. We characterized DA and GDVII derivatives adapted to grow on CHO-K1 cells. Expression of glycosaminoglycans did not influence infection of CHO-K1 cells by parental and adapted viruses. Mutations resulting from adaptation of DA and GDVII to CHO-K1 cells notably mapped to the well-characterized VP1 CD and VP2 EF loops of the capsid. Adaptation of the DA virus to CHO-K1 cells correlated with decreased sialic acid usage for entry. In contrast, adaptation of the GDVII virus to CHO-K1 cells correlated with the appearance of a weak sialic acid usage for entry. The sialic acid binding capacity of the GDVII variant resulted from a single amino acid mutation (VP1-51, Asn-->Ser) located out of the sialic acid binding region defined for virus DA. Mutations affecting tropism in vitro and sialic acid binding dramatically affected the persistence and neurovirulence of the viruses. 相似文献
196.
Maxime Pellegrin Jean-Fran?ois Aubert Karima Bouzourène Catherine Amstutz Lucia Mazzolai 《PloS one》2015,10(11)
We have previously demonstrated that exercise training prevents the development of Angiotensin (Ang) II-induced atherosclerosis and vulnerable plaques in Apolipoprotein E-deficient (ApoE-/-) mice. In this report, we investigated whether exercise attenuates progression and promotes stability in pre-established vulnerable lesions. To this end, ApoE-/- mice with already established Ang II-mediated advanced and vulnerable lesions (2-kidney, 1-clip [2K1C] renovascular hypertension model), were subjected to sedentary (SED) or voluntary wheel running training (EXE) regimens for 4 weeks. Mean blood pressure and plasma renin activity did not significantly differ between the two groups, while total plasma cholesterol significantly decreased in 2K1C EXE mice. Aortic plaque size was significantly reduced by 63% in 2K1C EXE compared to SED mice. Plaque stability score was significantly higher in 2K1C EXE mice than in SED ones. Aortic ICAM-1 mRNA expression was significantly down-regulated following EXE. Moreover, EXE significantly down-regulated splenic pro-inflammatory cytokines IL-18, and IL-1β mRNA expression while increasing that of anti-inflammatory cytokine IL-4. Reduction in plasma IL-18 levels was also observed in response to EXE. There was no significant difference in aortic and splenic Th1/Th2 and M1/M2 polarization markers mRNA expression between the two groups. Our results indicate that voluntary EXE is effective in slowing progression and promoting stabilization of pre-existing Ang II-dependent vulnerable lesions by ameliorating systemic inflammatory state. Our findings support a therapeutic role for voluntary EXE in patients with established atherosclerosis. 相似文献
197.
Karima Azdad Marcelo Chàvez Patrick Don Bischop Pim Wetzelaer Bart Marescau Peter Paul De Deyn David Gall Serge N. Schiffmann 《PloS one》2009,4(9)
The striatum is the major input structure of basal ganglia and is involved in adaptive control of behaviour through the selection of relevant informations. Dopaminergic neurons that innervate striatum die in Parkinson disease, leading to inefficient adaptive behaviour. Neuronal activity of striatal medium spiny neurons (MSN) is modulated by dopamine receptors. Although dopamine signalling had received substantial attention, consequences of dopamine depletion on MSN intrinsic excitability remain unclear. Here we show, by performing perforated patch clamp recordings on brain slices, that dopamine depletion leads to an increase in MSN intrinsic excitability through the decrease of an inactivating A-type potassium current, I
A. Despite the large decrease in their excitatory synaptic inputs determined by the decreased dendritic spines density and the increase in minimal current to evoke the first EPSP, this increase in intrinsic excitability resulted in an enhanced responsiveness to their remaining synapses, allowing them to fire similarly or more efficiently following input stimulation than in control condition. Therefore, this increase in intrinsic excitability through the regulation of I
A represents a form of homeostatic plasticity allowing neurons to compensate for perturbations in synaptic transmission and to promote stability in firing. The present observations show that this homeostatic ability to maintain firing rates within functional range also occurs in pathological conditions, allowing stabilizing neural computation within affected neuronal networks. 相似文献
198.
Immunity against the pre-erythrocytic stages of malaria is the most promising, as it is strong and fully sterilizing. Yet, the underlying immune effectors against the human Plasmodium falciparum pre-erythrocytic stages remain surprisingly poorly known and have been little explored, which in turn prevents any rational vaccine progress. Evidence that has been gathered in vitro and in vivo, in higher primates and in humans, is reviewed here, emphasizing the significant role of IFN-γ, either as a critical immune mediator or at least as a valuable surrogate marker of protection. One may hope that these results will trigger investigations in volunteers immunized either by optimally irradiated or over-irradiated sporozoites, to quickly delineate better surrogates of protection, which are essential for the development of a successful malaria vaccine. 相似文献
199.
Chedliya Ghemari Christophe Waterlot Anas Ayari Francis Douay Karima Nasri-Ammar 《人类与生态风险评估》2020,26(5):1270-1284
AbstractThe current study reports the effects of heavy metals issued from the emissions of phosphate and their bioaccumulation in the soils, leaf litter, and the terrestrial isopod Porcellionides pruinosus in the vicinity of Gabes-Ghannouch industrial complex. Cd, Pb, Zn, and Cu concentrations were measured in soils, leaf litter, and P. pruinosus individuals, collected from four stations located at different distances from the factory. Results showed that heavy metal concentrations in soils varied from one site to another and did not reflect those measured in individuals. In contrast, a positive correlation was found between the isopods’ body length and the distance from the pollution source, revealing the isopod sensitivity to the soil metal concentrations. The bioaccumulation factor was calculated using soil and leaf litter as a solid support with the aim of ordering the metal accumulation in P. pruinosus for each site. Overall, P. pruinosus could be defined as a macroconcentrator of Cd, Zn, and Cu (BAF?>?2) and as a deconcentrator of Pb (BAF?<?1). 相似文献
200.
Mouna Sahnoun Belgacem Naili Fatma Elgharbi Radhouane Kammoun Karima Gabsi Samir Bejar 《Biologia》2013,68(5):808-815
An optimum Aspergillus oryzae CBS 819.72 α-amylase production in a laboratory-scale fermentor using a wheat grinding by-product as a sole carbon source (340 U/mL) was obtained after 48 h of batch fermentation under an agitation rate of 900 rpm and a pH maintained constant for 24 h. The application of this α-amylase preparation at an adequate concentration showed positive effects on dough properties and bread quality. Extensographic analysis revealed that while this addition induced a significant increase in maximal dough resistance to extension and area below the curve (energy), it brought a substantial decrease in extensibility. Farinographic results revealed small decreases in terms of time development, water absorption, and dough stability. Bread volume was also observed to undergo a significant increase. 相似文献