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31.
Fran?ois Briand Morgan Tréguier Agnès André Didier Grillot Marc Issandou Khadija Ouguerram Thierry Sulpice 《Journal of lipid research》2010,51(4):763-770
Liver X receptor (LXR) activation promotes reverse cholesterol transport (RCT) in rodents but has major side effects (increased triglycerides and LDL-cholesterol levels) in species expressing cholesteryl ester transfer protein (CETP). In the face of dyslipidemia, it remains unclear whether LXR activation stimulates RCT in CETP species. We therefore used a hamster model made dyslipidemic with a 0.3% cholesterol diet and treated with vehicle or LXR agonist GW3965 (30 mg/kg bid) over 10 days. To investigate RCT, radiolabeled 3H-cholesterol macrophages or 3H-cholesteryl oleate-HDL were then injected to measure plasma and feces radioactivity over 72 or 48 h, respectively. The cholesterol-enriched diet increased VLDL-triglycerides and total cholesterol levels in all lipoprotein fractions and strongly increased liver lipids. Overall, GW3965 failed to improve both dyslipidemia and liver steatosis. However, after 3H-cholesterol labeled macrophage injection, GW3965 treatment significantly increased the 3H-tracer appearance by 30% in plasma over 72 h, while fecal 3H-cholesterol excretion increased by 156% (P < 0.001). After 3H-cholesteryl oleate-HDL injection, GW3965 increased HDL-derived cholesterol fecal excretion by 64% (P < 0.01 vs. vehicle), while plasma fractional catabolic rate remained unchanged. Despite no beneficial effect on dyslipidemia, LXR activation promotes macrophage-to-feces RCT in dyslipidemic hamsters. These results emphasize the use of species with a more human-like lipoprotein metabolism for drug profiling. 相似文献
32.
W Richard Mukabana Khadija Kannady G Michael Kiama Jasper N Ijumba Evan M Mathenge Ibrahim Kiche Gamba Nkwengulila Leonard Mboera Deo Mtasiwa Yoichi Yamagata Ingeborg van Schayk Bart GJ Knols Steven W Lindsay Marcia Caldas de Castro Hassan Mshinda Marcel Tanner Ulrike Fillinger Gerry F Killeen 《Malaria journal》2006,5(1):1-14
Background
Malaria imposes significant costs on households and the poor are disproportionately affected. However, cost data are often from quantitative surveys with a fixed recall period. They do not capture costs that unfold slowly over time, or seasonal variations. Few studies investigate the different pathways through which malaria contributes towards poverty. In this paper, a framework indicating the complex links between malaria, poverty and vulnerability at the household level is developed and applied using data from rural Kenya.Methods
Cross-sectional surveys in a wet and dry season provide data on treatment-seeking, cost-burdens and coping strategies (n = 294 and n = 285 households respectively). 15 case study households purposively selected from the survey and followed for one year provide in-depth qualitative information on the links between malaria, vulnerability and poverty.Results
Mean direct cost burdens were 7.1% and 5.9% of total household expenditure in the wet and dry seasons respectively. Case study data revealed no clear relationship between cost burdens and vulnerability status at the end of the year. Most important was household vulnerability status at the outset. Households reporting major malaria episodes and other shocks prior to the study descended further into poverty over the year. Wealthier households were better able to cope.Conclusion
The impacts of malaria on household economic status unfold slowly over time. Coping strategies adopted can have negative implications, influencing household ability to withstand malaria and other contingencies in future. To protect the poor and vulnerable, malaria control policies need to be integrated into development and poverty reduction programmes. 相似文献33.
El Hadri K Glorian M Monsempes C Dieudonné MN Pecquery R Giudicelli Y Andreani M Dugail I Fève B 《The Journal of biological chemistry》2004,279(15):15130-15141
34.
Mounaji K Erraiss NE Iddar A Wegnez M Serrano A Soukri A 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,131(3):411-421
The NAD(+)-dependent cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) has been purified to homogeneity from skeletal muscle of the newt Pleurodeles waltl (Amphibia, Urodela). The purification procedure including ammonium sulfate fractionation followed by Blue Sepharose CL-6B chromatography resulted in a 24-fold increase in specific activity and a final yield of approximately 46%. The native protein exhibited an apparent molecular weight of approximately 146 kDa with absolute specificity for NAD(+). Only one GAPDH isoform (pI 7.57) was obtained by chromatofocusing. The enzyme is an homotetrameric protein composed of identical subunits with an apparent molecular weight of approximately 37 kDa. Monospecific polyclonal antibodies raised in rabbits against the purified newt GAPDH immunostained a single 37-kDa GAPDH band in extracts from different tissues blotted onto nitrocellulose. A 510-bp cDNA fragment that corresponds to an internal region of a GapC gene was obtained by RT-PCR amplification using degenerate primers. The deduced amino acid sequence has been used to establish the phylogenetic relationships of the Pleurodeles enzyme--the first GAPDH from an amphibian of the Caudata group studied so far--with other GAPDHs of major vertebrate phyla. 相似文献
35.
Jér?me Le Bloc'h Véronique Leray Hassan Nazih Olivier Gauthier Samuel Serisier Thierry Magot Michel Krempf Patrick Nguyen Khadija Ouguerram 《PloS one》2015,10(9)
Aim
Nicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA) on lipids and high-density lipoprotein (HDL) cholesteryl ester (CE) turnover in obese Insulin-Resistant dogs with increase plasma triglycerides.Methods
HDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA-treated dogs was also measured.Results
NA reduced plasma total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG), and very-low-density lipoprotein TG concentrations (p < 0.05). The kinetic study also showed a higher cholesterol esterification rate (p < 0.05). HDL-CE turnover was accelerated (p < 0.05) via HDL removal through endocytosis and selective CE uptake (p < 0.05). We measured an elevated in vitro cell cholesterol efflux (p < 0.05) with NA treatment in accordance with a higher cholesterol esterification.Conclusion
NA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile. 相似文献36.
The Corynebacterium glutamicum mycothiol peroxidase is a reactive oxygen species‐scavenging enzyme that shows promiscuity in thiol redox control
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Brandán Pedre Inge Van Molle Almudena F. Villadangos Khadija Wahni Didier Vertommen Lucía Turell Huriye Erdogan Luis M. Mateos Joris Messens 《Molecular microbiology》2015,96(6):1176-1191
Cysteine glutathione peroxidases (CysGPxs) control oxidative stress levels by reducing hydroperoxides at the expense of cysteine thiol (‐SH) oxidation, and the recovery of their peroxidatic activity is generally accomplished by thioredoxin (Trx). Corynebacterium glutamicum mycothiol peroxidase (Mpx) is a member of the CysGPx family. We discovered that its recycling is controlled by both the Trx and the mycothiol (MSH) pathway. After H2O2 reduction, a sulfenic acid (‐SOH) is formed on the peroxidatic cysteine (Cys36), which then reacts with the resolving cysteine (Cys79), forming an intramolecular disulfide (S‐S), which is reduced by Trx. Alternatively, the sulfenic acid reacts with MSH and forms a mixed disulfide. Mycoredoxin 1 (Mrx1) reduces the mixed disulfide, in which Mrx1 acts in combination with MSH and mycothiol disulfide reductase as a biological relevant monothiol reducing system. Remarkably, Trx can also take over the role of Mrx1 and reduce the Mpx‐MSH mixed disulfide using a dithiol mechanism. Furthermore, Mpx is important for cellular survival under H2O2 stress, and its gene expression is clearly induced upon H2O2 challenge. These findings add a new dimension to the redox control and the functioning of CysGPxs in general. 相似文献
37.
Johan M. J. Van den Bergh Khadija Guerti Yannick Willemen Eva Lion Nathalie Cools Herman Goossens Alex Vorsters Viggo F. I. Van Tendeloo Sébastien Anguille Pierre Van Damme Evelien L. J. M. Smits 《Journal of cellular and molecular medicine》2014,18(7):1372-1380
Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells. 相似文献
38.
Sharmilee Gnanapavan Peggy Ho Wendy Heywood Sam Jackson Donna Grant Khadija Rantell Geoff Keir Kevin Mills Lawrence Steinman Gavin Giovannoni 《Journal of neurochemistry》2013,125(5):766-773
Multiple sclerosis (MS) is a CNS disorder characterized by demyelination and neurodegeneration. Although hallmarks of recovery (remyelination and repair) have been documented in early MS, the regenerative capacity of the adult CNS per se remains uncertain with the wide held belief that it is either limited or non‐existent. The neural cell adhesion molecule (NCAM) is a cell adhesion molecule that has been widely implicated in axonal outgrowth, guidance and fasciculation. Here, we used in vitro and in vivo of MS to investigate the role of NCAM in disease progression. We show that in health NCAM levels decrease over time, but this occurs acutely after demyelination and remains reduced in chronic disease. Our findings suggest that depletion of NCAM is one of the factors associated with or possibly responsible for disease progression in MS. 相似文献
39.
Syed Adnan Ali Shah Sadia Sultan Normahanim Binti Hassan Fauzia Khadija Binti Muhammad Muhammad Afifi Bin Mohd Faridz Fatimah BeBe M. Hussain Munawar Hussain Humera Syed Adnan 《Steroids》2013
Structural modification of steroids through whole-cell biocatalysis is an invaluable procedure for the production of active pharmaceutical ingredients (APIs) and key intermediates. Modifications could be carried out with regio- and stereospecificity at positions hardly available for chemical agents. Much attention has been focused recently on the biotransformation of 17α-ethynyl substituted steroidal drugs using fungi, bacteria and plant cell cultures in order to obtained novel biologically active compounds with diverse structure features. Present article includes studies on biotransformation on 17α-ethynyl substituted steroidal drugs using microorganisms and plant cell cultures. Various experimental and structural elucidation methods used in biotransformational processes are also highlighted. 相似文献
40.
Ravaux L Denoyelle C Monne C Limon I Raymondjean M El Hadri K 《Molecular and cellular biology》2007,27(23):8374-8387