2,205 research outputs found

    Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation

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    Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety

    Reevaluation of the phylogenetic relationship between Mobilid and Sessilid peritrichs (Ciliophora, Oligohymenophorea) based on small subunit rRNA genes sequences

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    Based on morphological characters, peritrich ciliates (Class Olygohymenophorea, Subclass Peritrichia) have been subdivided into the Orders Sessilida and Mobilida. Molecular phylogenetic studies on peritrichs have been restricted to members of the Order Sessilida. In order to shed more light into the evolutionary relationships within peritrichs, the complete small subunit rRNA (SSU rRNA) sequences of four mobilid species, Trichodina nobilis, Trichodina heterodentata, Trichodina reticulata, and Trichodinella myakkae were used to construct phylogenetic trees using maximum parsimony, neighbor joining, and Bayesian analyses. Whatever phylogenetic method used, the peritrichs did not constitute a monophyletic group: mobilid and sessilid species did not cluster together. Similarity in morphology but difference in molecular data led us to suggest that the oral structures of peritrichs are the result of evolutionary convergence. In addition, Trichodina reticulata, a Trichodina species with granules in the center of the adhesive disc, branched separately from its congeners, Trichodina nobilis and Trichodina heterodentata, trichodinids without such granules. This indicates that granules in the adhesive disc might be a phylogenetic character of high importance within the Family Trichodinidae.Based on morphological characters, peritrich ciliates (Class Olygohymenophorea, Subclass Peritrichia) have been subdivided into the Orders Sessilida and Mobilida. Molecular phylogenetic studies on peritrichs have been restricted to members of the Order Sessilida. In order to shed more light into the evolutionary relationships within peritrichs, the complete small subunit rRNA (SSU rRNA) sequences of four mobilid species, Trichodina nobilis, Trichodina heterodentata, Trichodina reticulata, and Trichodinella myakkae were used to construct phylogenetic trees using maximum parsimony, neighbor joining, and Bayesian analyses. Whatever phylogenetic method used, the peritrichs did not constitute a monophyletic group: mobilid and sessilid species did not cluster together. Similarity in morphology but difference in molecular data led us to suggest that the oral structures of peritrichs are the result of evolutionary convergence. In addition, Trichodina reticulata, a Trichodina species with granules in the center of the adhesive disc, branched separately from its congeners, Trichodina nobilis and Trichodina heterodentata, trichodinids without such granules. This indicates that granules in the adhesive disc might be a phylogenetic character of high importance within the Family Trichodinidae

    Bis[μ-2-(2-benzoyl­hydrazinylidenemeth­yl)-6-methoxy­phenolato][2-(2-benzoyl­hydrazinylidenemeth­yl)-6-methoxy­phenolato]dimanganese(II) perchlorate methanol solvate

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    In the title complex, [Mn2(C15H13N2O3)3]ClO4·CH3OH, the two MnII ions are bridged by two phenolate O atoms from two ligands, forming an Mn2O2 quadrangle. Each MnII ion has a distorted octa­hedral coordination geometry. One MnII ion is coordinated by two N atoms and four O atoms from two ligands, and the other is coordinated by one N atom and five O atoms from three ligands. A dimer is formed by inter­molecular N—H⋯O hydrogen bonds. The dimers, perchlorate anions and methanol solvent mol­ecules are further connected into a chain along [01] through N—H⋯O and O—H⋯O hydrogen bonds

    The iNOS/Src/FAK axis is critical in Toll-like receptor-mediated cell motility in macrophages

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    AbstractThe Toll-like receptors (TLRs) play a pivotal role in innate immunity for the detection of highly conserved, pathogen-expressed molecules. Previously, we demonstrated that lipopolysaccharide (LPS, TLR4 ligand)-increased macrophage motility required the participation of Src and FAK, which was inducible nitric oxide synthase (iNOS)-dependent. To investigate whether this iNOS/Src/FAK pathway is a general mechanism for macrophages to mobilize in response to engagement of TLRs other than TLR4, peptidoglycan (PGN, TLR2 ligand), polyinosinic–polycytidylic acid (polyI:C, TLR3 ligand) and CpG-oligodeoxynucleotides (CpG, TLR9 ligand) were used to treat macrophages in this study. Like LPS stimulation, simultaneous increase of cell motility and Src (but not Fgr, Hck, and Lyn) was detected in RAW264.7, peritoneal macrophages, and bone marrow-derived macrophages exposed to PGN, polyI:C and CpG. Attenuation of Src suppressed PGN-, polyI:C-, and CpG-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by the reintroduction of siRNA-resistant Src. Besides, knockdown of FAK reduced the mobility of macrophages stimulated with anyone of these TLR ligands. Remarkably, PGN-, polyI:C-, and CpG-induced Src expression, FAK Pi-Tyr861, and cell mobility were inhibited in macrophages devoid of iNOS, indicating the importance of iNOS. These findings corroborate that iNOS/Src/FAK axis occupies a central role in macrophage locomotion in response to engagement of TLRs

    Associations between impulsivity, aggression, and suicide in Chinese college students

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    BACKGROUND: Although there are accumulating data regarding the epidemiology of suicide in China, there are meager data on suicidal ideation and attempts among college students. Interestingly, elevated impulsivity is thought to facilitate the transition from suicidal thoughts to suicidal behavior. Therefore, the objective of this research was to identify the associations between suicide and the personality factors of impulsivity and aggression. METHODS: This study’s sampling method employed stratified random cluster sampling. A multi-stage stratified sampling procedure was used to select participants (n = 5,245). We conducted structured interviews regarding a range of socio-demographic characteristics and suicidal morbidity. The Patient Health Questionnaire depression module (PHQ-9) was used to acquire the information about thoughts of being better off dead or hurting themselves in some ways during the past two weeks. The impulsivity symptoms in this study were assessed with the BIS-11-CH (i.e., the Chinese version of the BIS-11), and the Aggressive symptoms were assessed with the BAQ. The statistical package for social science (SPSS) v.13.0 program (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Socio-demographic variables such as ethnic and gender were compared between groups, through the use of χ(2) tests. The nonparametric test (k Independent Sample test, Kruskal-Wallis H) was performed to determine differences between the personality factors of impulsivity and aggression and suicide. RESULTS: In total, 9.1% (n = 479) of the 5,245 students reported they have ever thought about committing suicide; and 1% (n = 51) reported a history of attempted suicide (attempters). The analyses detected significant differences in scores on cognitive impulsivity (p < 0.01), when comparing individuals who only had suicidal ideation and individuals who had attempted suicide. Moreover, significant differences were found between ideators only and attempters on scores of self-oriented attack (p < .001). CONCLUSIONS: Suicidal ideation is prevalent among Chinese university students. Students with high aggression scores were more susceptible to committing suicide. Scores on self-oriented attack and cognitive impulsivity may be important factors for differentially predicting suicide ideation and suicide attempts

    Electrical transport properties of an isolated CdS microrope composed of twisted nanowires

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    CdS is one of the important II-VI group semiconductors. In this paper, the electrical transport behavior of an individual CdS microrope composed of twisted nanowires is studied. It is found that the current–voltage (I-V) characteristics show two distinct power law regions from 360 down to 60 K. Space-charge-limited current (SCLC) theory is used to explain these temperature- and electric-field-dependent I-V curves. The I-V data can be well fitted by this theory above 100 K, and the corresponding carrier mobility, trap energy, and trap concentration are also obtained. However, the I-V data exhibit some features of the Coulomb blockade effect below 80 K
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