1,692 research outputs found

    Enrichment of rare alleles within epigenetic chromatin marks in the first intron

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    In previous studies, we demonstrated that some sites in the first intron likely regulate gene expression. In the present work, we sought to further confirm the functional relevance of first intron sites by estimating the quantity of rare alleles in the first intron. A basic hypothesis posited herein is that genomic regions carrying more functionally important sites will have a higher proportion of rare alleles. We estimated the proportions of rare single nucleotide polymorphisms with a minor allele frequency < 0.01 located in several histone marks in the first introns of various genes, and compared them with those in other introns and those in 2-kb upstream regions. As expected, rare alleles were found to be significantly enriched in most of the regulatory sites located in the first introns. Meanwhile, transcription factor binding sites were significantly more enriched in the 2-kb upstream regions (i.e., the regions of putative promoters of genes) than in the first introns. These results strongly support our proposal that the first intron sites of genes may have important regulatory functions in gene expression independent of promoters

    Effect of software version and parameter settings on the marginal and internal adaptation of crowns fabricated with the CAD/CAM system

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    Objective This study investigated the marginal and internal adaptation of individual dental crowns fabricated using a CAD/CAM system (Sirona’s BlueCam), also evaluating the effect of the software version used, and the specific parameter settings in the adaptation of crowns.Material and Methods Forty digital impressions of a master model previously prepared were acquired using an intraoral scanner and divided into four groups based on the software version and on the spacer settings used. The versions 3.8 and 4.2 of the software were used, and the spacer parameter was set at either 40 μm or 80 μm. The marginal and internal fit of the crowns were measured using the replica technique, which uses a low viscosity silicone material that simulates the thickness of the cement layer. The data were analyzed using a Friedman two-way analysis of variance (ANOVA) and paired t-tests with significance level set at

    The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs

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    Wild Panax ginseng C.A. Meyer (WG) is a well-known medicinal herb. In this study, the protective effects of a water extract from the root of WG on benzo[alpha]pyrene (BP)-induced hepatotoxicity and the mechanism of these effects were investigated for the first time. The effects of WG on liver toxicities induced by BP were assessed by blood biochemical and histopathological analyses. BP caused severe liver injury in rats, as indicated by elevated plasma ALT, AST and LPO levels. Pretreatment with WG for 4 weeks completely abrogated increases in the ALT, AST and LPO levels when challenged with BP. Reductions in GSH content and GST activity by BP were reversed by WG. These protective effects of WG against BP-induced toxicity were consistent with the results of histopathological examinations. We next examined the effects of WG on the gene expression of the enzymes that metabolize BP in H4IIE cells. CYP1A1 mRNA and protein expression were increased by BP. WG moderately inhibited BP-induced CYP1A1 gene expression. Moreover, GSTA2, GSTA3 and GSTM2 gene expressions were significantly increased by WG through the Nrf2/antioxidant responsive element pathway for enzyme induction. In summary, WG is efficacious in protecting against BP-induced hepatotoxicity as results of metabolic regulations through both the inhibition of metabolic enzyme activation and the enhancement of electrophilic detoxification, implying that WG should be considered a potential chemopreventive agent

    Spinal Cord Tumors of the Thoracolumbar Junction Requiring Surgery: A Retrospective Review of Clinical Features and Surgical Outcome

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    PURPOSE: A retrospective review of medical records and imaging studies. To investigate characteristic clinical features and surgical outcomes of spinal cord tumors (SCTs) of the thoracolumbar junction (TLJ). The spinal cord transitions to the cauda equina in the TLJ. The TLJ contains the upper and lower motor neurons of the spinal cord and cauda equina. As a result, the clinical features of lesions in the TLJ vary, and these anatomical characteristics may affect surgical outcome. MATERIALS AND METHODS: Pathological diagnosis, clinical features, neurological signs, and surgical outcomes were investigated in 76 patients surgically treated at our institute for SCTs arising from T11 to L2. The patients were divided into epiconus (T11-12, n=18) and conus groups (L1-2, n=58). RESULTS: Patients in the epiconus group had hyperactive deep tendon reflexes (DTRs), while those in the conus group had hypoactive DTRs (p < 0.05). Nine patients were misdiagnosed with intervertebral disc diseases (IVDs) before correct diagnoses were made. It was impossible to definitively determine the exact cause of symptoms in four patients who had both SCTs and IVDs. CONCLUSION: Among SCTs of the TLJ, the epiconus group displayed upper motor neuron syndrome and the conus group displayed lower motor neuron syndrome. SCTs of the TLJ were frequently misdiagnosed as IVDs due to symptomatic similarities. SCTs of the TLJ should be included in differential diagnosis of back and leg pain, and it is highly recommended that routine lumbar magnetic resonance imaging include the TLJ.ope

    Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons

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    <p>Abstract</p> <p>Background</p> <p>Proanthocyanidin is a polyphenolic bioflavonoid with known antioxidant activity. Some flavonoids have a modulatory effect on [Ca<sup>2+</sup>]<sub>i</sub>. Although proanthocyanidin extract from blueberries reportedly affects Ca<sup>2+ </sup>buffering capacity, there are no reports on the effects of proanthocyanidin on glutamate-induced [Ca<sup>2+</sup>]<sub>i </sub>or cell death. In the present study, the effects of grape seed proanthocyanidin extract (GSPE) on glutamate-induced excitotoxicity was investigated through calcium signals and nitric oxide (NO) in cultured rat hippocampal neurons.</p> <p>Results</p> <p>Pretreatment with GSPE (0.3-10 μg/ml) for 5 min inhibited the [Ca<sup>2+</sup>]<sub>i </sub>increase normally induced by treatment with glutamate (100 μM) for 1 min, in a concentration-dependent manner. Pretreatment with GSPE (6 μg/ml) for 5 min significantly decreased the [Ca<sup>2+</sup>]<sub>i </sub>increase normally induced by two ionotropic glutamate receptor agonists, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). GSPE further decreased AMPA-induced response in the presence of 1 μM nimodipine. However, GSPE did not affect the 50 mM K<sup>+</sup>-induced increase in [Ca<sup>2+</sup>]<sub>i</sub>. GSPE significantly decreased the metabotropic glutamate receptor agonist (<it>RS</it>)-3,5-Dihydroxyphenylglycine-induced increase in [Ca<sup>2+</sup>]<sub>i</sub>, but it did not affect caffeine-induced response. GSPE (0.3-6 μg/ml) significantly inhibited synaptically induced [Ca<sup>2+</sup>]<sub>i </sub>spikes by 0.1 mM [Mg<sup>2+</sup>]<sub>o</sub>. In addition, pretreatment with GSPE (6 μg/ml) for 5 min inhibited 0.1 mM [Mg<sup>2+</sup>]<sub>o</sub>- and glutamate-induced formation of NO. Treatment with GSPE (6 μg/ml) significantly inhibited 0.1 mM [Mg<sup>2+</sup>]<sub>o</sub>- and oxygen glucose deprivation-induced neuronal cell death.</p> <p>Conclusions</p> <p>All these data suggest that GSPE inhibits 0.1 mM [Mg<sup>2+</sup>]<sub>o</sub>- and oxygen glucose deprivation-induced neurotoxicity through inhibition of calcium signals and NO formation in cultured rat hippocampal neurons.</p
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