Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 5 Articles
This study investigated the effects of ?-alanine\n(BA) ingestion on the behavioral and neuroendocrine\nresponse of post-traumatic stress disorder (PTSD) in a\nmurine model. Animals were fed a normal diet with or without\n(PL) BA supplementation (100 mg kg?1) for 30 days.\nAnimals were then exposed to a predator-scent stress (PSS)\nor a sham (UNEX). Behaviors were evaluated using an elevated\nplus maze (EPM) and acoustic startle response (ASR)\n7 days following exposure to the PSS. Corticosterone concentrations\n(CS), expression of brain-derived neurotrophic\nfactor (BDNF), and brain carnosine concentrations were\nanalyzed a day later. Animals in PSS+PL spent significantly\nless time in the open arms and in the number of entries in\nthe EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals\nin PSS+BA had comparable scores to UNEX+BA.\nAnxiety index was higher (p < 0.05) in PSS+PL compared\nto PSS+BA or animals that were unexposed. ASR\nand freezing were greater (p < 0.05) in animals exposed to\nPSS compared to animals unexposed. CS expression was higher (p < 0.05) in animals exposed to PSS compared to\nunexposed animals. Brain carnosine concentrations in the\nhippocampus and other brain sections were significantly\ngreater in animals supplemented with BA compared to PL.\nBDNF expression in the CA1 and DG subregions of the\nhippocampus was lower (p < 0.05) in animals exposed and\nfed a normal diet compared to animals exposed and supplemented\nwith BA, or animals unexposed. In conclusion,\nBA supplementation in rats increased brain carnosine concentrations\nand resulted in a reduction in PTSD-like behavior,\nwhich may be mediated in part by maintaining BDNF\nexpression in the hippocampus....
Gene targeting is a critical tool for construction\nof disease models. However, the application\nof traditional homologous recombination-mediated\ngene knockout technology is limited by the absence\nof rapid frequency-guaranteed targeting methods.\nAlthough conventional small hairpin RNA (shRNA)-\nmediated gene silencing offers an alternative for gene\ntargeting, its application is frequently compromised by\nlower expression efficiency via RNA interference\ncompared to gene knockout. Here we provide an\nefficient gene targeting strategy involving drug-inducible\nsynergistic silencing with multiple shRNA molecules.\nOn induction, the levels of the target proteins\ndecreased to undetectable levels in all the tested stable\ntransgenic mammalian cell lines, including HEK293\nand embryonic stem cell-derived progenies carrying\nshRNA silencing cassettes. In a transgenic mouse\nmodel carrying a silencing cassette targeting the\nrhodopsin gene, short-time inducer treatment was\nsufficient to ablate the rhodopsin protein in the retina,\nresulting in similar retinal phenotypic changes as those\nobserved in rhodopsin mutant mice. Therefore, on a\nbroad basis, this inducible shRNA gene targeting\nstrategy offers a true gene knockout alternative comparable\nto conventional RNA interference approaches....
Obesity is a global epidemic and a causal factor for many serious ailments and is increasing at alarming rates. Obesity is responsible for about 5% deaths with global economic impact of $2 trillion annually. Flaxseed has great ethnopharmacological relevance. Because of the lipid lowering profile of its constituents it can be used for treatment of Obesity. Flaxseed, a nutraceutical rich in polyunsaturated fatty acids, lignans and dietary fibres. Zebrafish (Danio rerio) has come to attention recently as a genetically tractable vertebrate model system for human diseases. Organs and tissues of zebrafish and humans are structurally and functionally quite similar. Flaxseed may have potential antiobesity activity which can be best evaluated by using zebrafish model of diet induced obesity. Flaxseeds were collected, cleaned, ground to powder and extracted with petroleum ether to collect oil. The defatted powder remaining behind was dried and re-extracted with ethanol:water (7:3 v/v) to collect lignan i.e. secoisolariciresinol diglucoside. The different constituents of flaxseed such as oil, lignan, oil/lignan emulsion and powder were administered to zebrafish and further they were evaluated and compared for their antiobesity potential with orlistat as a standard. The study showed that there was significant restoration of obesogenic parameters in groups receiving flaxseed constituents. Restoration of obesogenic parameters was shown higher with flaxseed powder as compared to other constituents. The results thus obtained were suggestive of the flaxseed powder having better antiobesity potential than individual constituents probably due to synergism of all the constituents....
Purpose To investigate the effectiveness of a combination\nof 6-thioguanine (6-TG) and pralatrexate (PDX) in methylthioadenosine\nphosphorylase (MTAP)-deficient T-cell acute\nlymphoblastic leukemia (T-cell ALL).\nMethods CCRF-CEM (MTAP?/?) and Molt4 (MTAP+/+)\nT-cell ALL cell lines were treated with 6-TG or PDX and\nevaluated for efficacy 72 h later. NOD/SCID gamma mice\nbearing CEM or Molt4 xenografts were treated with 6-TG\nand PDX alone or in combination to evaluate antitumor\neffects.\nResults CEM cells were more sensitive to 6-TG and PDX\nin vitro than Molt4. In vivo, CEM cells were very sensitive\nto PDX and 6-TG, whereas Molt4 cells were highly\nresistant to 6-TG. A well-tolerated combination of PDX\nand 6-TG achieved significant tumor regression in CEM\nxenografts.\nConclusions The loss of MTAP expression may be therapeutically\nexploited in T-cell ALL. The combination of\n6-TG and PDX, with the inclusion of leucovorin rescue,\nallows for a safe and effective regimen in MTAP-deficient\nT-cell ALL....
The effects of tetanus toxin (TeNT) both in the\nspinal cord, in clinical tetanus, and in the brain, in experimental\nfocal epilepsy, suggest disruption of inhibitory\nsynapses. TeNT is a zinc protease with selectivity for\nVesicle Associated Membrane Protein (VAMP; previously\nsynaptobrevin), with a reported selectivity for VAMP2 in\nrats. We found spatially heterogeneous expression of\nVAMP1 and VAMP2 in the hippocampus. Inhibitory terminals\nin stratum pyramidale expressed significantly more\nVAMP1 than VAMP2, while glutamatergic terminals in\nstratum radiatum expressed significantly more VAMP2\nthan VAMP1. Intrahippocampal injection of TeNT at doses\nthat induce epileptic foci cleaved both isoforms in tissue\naround the injection site. The cleavage was modest at\n2 days after injection and more substantial and extensive at\n8 and 16 days. Whole-cell recordings from CA1 pyramidal\ncells close to the injection site, made 8ââ?¬â??16 days after\ninjection, showed that TeNT decreases spontaneous EPSC\nfrequency to 38 % of control and VAMP2 immunoreactive\naxon terminals to 37 %. In contrast, TeNT almost completely\nabolished both spontaneous and evoked IPSCs\nwhile decreasing VAMP1 axon terminals to 45 %. We\nconclude that due to the functional selectivity of the toxin\nto the relative sparing of excitatory synaptic transmission\nshifts the network to pathogenically excitable state causing\nepilepsy....
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