Taking advantage of high-throughput sequencing technology, a large number of long noncoding RNAs (lncRNAs) have been recently characterized. Emerging evidence suggests that they play critical roles in diverse biolog...
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Taking advantage of high-throughput sequencing technology, a large number of long noncoding RNAs (lncRNAs) have been recently characterized. Emerging evidence suggests that they play critical roles in diverse biological processes, including the differentiation of skeletal muscle cells. As previous studies have focused mainly on the polyadenylated lncRNAs, the involvement of polyA-rninus IncRNAs in myocyte differentiation remains largely unexplored. To this aspect, their expression and regulation were examined in the present study. During the course of myocyte differentiation of C2C12 cells, polyA-minus RNAs were isolated and analyzed by RNA-seq. In addition to identifying 904 novel polyA-minus lncRNAs, their temporal expression was further characterized in this process. For many lncRNAs, differentiation-specific profiles were revealed. Based on their unique expression profiles, these lncRNAs were grouped into nine regulation categories. Taken together, our study greatly contributed to the identification of a dynamic regulation ofpolyA-minus lncRNAs, and clarified their potential roles in myocyte differentiation.
An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard (IS) was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deprotei...
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An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard (IS) was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deproteinated with 10% (v/v) perchloric acid. Separation was achieved on a UltimateTM AQ-C18 column (250 mm×4.6 mm, 5 μm) with a mobile phase (pH 5.05) composed of acetonitrile-water (31:69, v/v, containing 0.002 M sodium dodecyl sulfate, 0.0125 M potassium dihydrogen phosphate, 0.015 M triethylamine) at a flow rate of 1.0 mL/min. The calibration curve was linear (r〉0.994) between 7.5 and 4000 ng/mL. The lower limit of quantification (LLOQ) was 7.5 ng/mL. The precision was validated and the relative standard deviation was in the range of 1.87% to 15.70%; the accuracy was between 93.98%-106.89%. The mean recoveries were 95.40% and 95.31% for metformin and IS, respectively. The relative error (RE) of stability at different storage conditions was within ±9.00%. This method was used to determine the concentration-time profile of metformin in diabetic rat plasma following an oral administration of metformin at the dose of 10 mg/kg. Our results indicated that ion-pair HPLC-UV method using UltimateTM AQ-C18 column was effective for the pharmacokinetic studies of high polarity compounds like metformin.
Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochond...
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Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochondria-targeting agent, exhibits potential therapeutic effects for tumors. Based on the effects of DCA on tumor cellular metabolism, we carried out this study to investigate the anti-tumor activity of DCA in C6 glioma cells in vitro. The results showed that DCA was able to increase the activity of pyruvate dehydrogenase (PDH), induce the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP) in C6 ceils in vitro (P〈0.05 or 0.01), indicating that the anti-tumor effects of DCA in C6 cells could be through the activation of the mitochondrial pathway. In conclusion, mitochondria could be a viable therapeutic target for the treatment of glioma.
A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol (internal standard)...
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A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol (internal standard) were extracted from nude mice plasma samples by liquid-liquid extraction. Separation was achieved on a reversed phase ClS column with a mobile phase of acetonitrile-water (35:65, v/v) containing 5 mM ammonium formate (pH = 3.0). All compounds were monitored by mass spectrometry with electrospray positive ionization. The lower limit of quantification was 0.5 ng/mL for both erlotinib and OSI-420; accuracy was estimated by relative error, which was in the range from 0.07% to 8.00% for erlotinib and -2.83% to 6.67% for OSI-420; precision was validated by relative standard deviation, which was from 2.28% to 15.12% for erlotinib and from 1.96% to 11.50% for OSI-420. This method was applied to a pharmacokinetic study of BALB/c nude mice following oral administration of erlotinib at 12.5 mg/kg. A 2-compartment model was used to fit the pharmacokinetics of erlotinib and 1-compartment model for the pharmacokinetics of OSI-420. The ratio of the active metabolite to parent drug in mice was greater than previously reported in humans and probably reflects interspecies difference in the rate of conversion of erlotinib to OSI-420.
Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential r...
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Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential role. To explore the function of Dnmt1, its expression was first profiled during the course of adipocyte differentiation of 3T3-L1 cells. The results revealed a dynamic regulation of its expression at the initiation stage. Knockdown of Dnmt1 compromised the differentiation process and decreased lipid production within the cells. To the aspect of epigenetic regulation, promoter methylation of Cdkn1a was significantly increased at the initiation stage of the differentiation, accompanied by decreased Cdkn1a expression. Furthermore, knockdown of Dnmt1 led to an increased Cdkn1a expression, indicating that Dnmt1 inhibits Cdkn1a expression by promoter methylation. Furthermore, we found that knockdown of Cdkn1a up-regulated the expression of PPARγ and resulted in enhanced adipocyte differentiation. In summary, our results demonstrated that Dnmt1 regulated the process of adipogenesis by methylation of Cdkn1a promoter, suggesting that Cdkn1a played a fundamental role in the prevention of adipocyte hyperplasia.
We report a novel P-directing effect of imidazolium based ionic liquid,which was observed when we conducted the glycosylation of a 6-O-acetyl-2,3,4-tri-O-benzyl-mannose trichloroacetimidate donor with a modified ionic...
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We report a novel P-directing effect of imidazolium based ionic liquid,which was observed when we conducted the glycosylation of a 6-O-acetyl-2,3,4-tri-O-benzyl-mannose trichloroacetimidate donor with a modified ionic liquid support acceptor. The mechanism was investigated and a hypothesis was *** optimization of the reaction conditions,an innovative method for the selective construction of 1,2-cis-β-D-mannopyranosyl linkage was developed.
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