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  • 1
    Publication Date: 2018-08-11
    Description: Previous evidence has suggested that puerarin may attenuate cardiac hypertrophy; however, the potential mechanisms have not been determined. Moreover, the use of puerarin is limited by severe adverse events, including intravascular hemolysis. This study used a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy to evaluate the potential mechanisms underlying the attenuating efficacy of puerarin on cardiac hypertrophy, as well as the metabolic mechanisms of puerarin involved. We confirmed that puerarin (50 mg/kg per day) significantly attenuated cardiac hypertrophy, upregulated Nrf2, and decreased Keap1 in the myocardium. Moreover, puerarin significantly promoted Nrf2 nuclear accumulation in parallel with the upregulated downstream proteins, including heme oxygenase 1, glutathione transferase P1, and NAD(P)H:quinone oxidoreductase 1. Similar results were obtained in neonatal rat cardiomyocytes (NRCMs) treated with angiotensin II (Ang II; 1 μ M) and puerarin (100 μ M), whereas the silencing of Nrf2 abolished the antihypertrophic effects of puerarin. The mRNA and protein levels of UGT1A1 and UGT1A9, enzymes for puerarin metabolism, were significantly increased in the liver and heart tissues of AAC rats and Ang II–treated NRCMs. Interestingly, the silencing of Nrf2 attenuated the puerarin-induced upregulation of UGT1A1 and UGT1A9. The results of chromatin immunoprecipitation-quantitative polymerase chain reaction indicated that the binding of Nrf2 to the promoter region of Ugt1a1 or Ugt1a9 was significantly enhanced in puerarin-treated cardiomyocytes. These results suggest that Nrf2 is the key regulator of antihypertrophic effects and upregulation of the metabolic enzymes UGT1A1 and UGT1A9 of puerarin. The autoregulatory circuits between puerarin and Nrf2-induced UGT1A1/1A9 are beneficial to attenuate adverse effects and maintain the pharmacologic effects of puerarin.
    Print ISSN: 0022-3565
    Electronic ISSN: 1521-0103
    Topics: Medicine
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  • 2
    Publication Date: 2018-05-31
    Description: Author(s): P. Shahi, D. J. Singh, J. P. Sun, L. X. Zhao, G. F. Chen, Y. Y. Lv, J. Li, J.-Q. Yan, D. G. Mandrus, and J.-G. Cheng A new analysis shows that the topological material ZrTe 5 is a semiconductor with a unique electronic structure that exhibits very different behavior for electrons and holes, providing a long-sought explanation for its mysterious resistivity peak. [Phys. Rev. X 8, 021055] Published Wed May 30, 2018
    Electronic ISSN: 2160-3308
    Topics: Physics
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  • 3
    Publication Date: 2018-06-29
    Description: Chiral amines are widely used as catalysts in asymmetric synthesis to activate carbonyl groups for α-functionalization. Carbonyl catalysis reverses that strategy by using a carbonyl group to activate a primary amine. Inspired by biological carbonyl catalysis, which is exemplified by reactions of pyridoxal-dependent enzymes, we developed an N-quaternized pyridoxal catalyst for the asymmetric Mannich reaction of glycinate with aryl N -diphenylphosphinyl imines. The catalyst exhibits high activity and stereoselectivity, likely enabled by enzyme-like cooperative bifunctional activation of the substrates. Our work demonstrates the catalytic utility of the pyridoxal moiety in asymmetric catalysis.
    Keywords: Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2018-10-20
    Description: Targeting enhancer of zeste homolog 2 protects against acute kidney injury Targeting enhancer of zeste homolog 2 protects against acute kidney injury, Published online: 19 October 2018; doi:10.1038/s41419-018-1012-0 Targeting enhancer of zeste homolog 2 protects against acute kidney injury
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2018-04-12
    Description: Hollow lanthanide-doped compounds are some of the most popular materials for high-performance luminescent devices. However, it is challenging to find an approach that can fabricate large-scale and well-crystallized lanthanide-doped hollow structures and that is facile, efficient and of low cost. In this study, YBO 3 : Eu 3+ /Tb 3+ hollow microspheres were fabricated by using a novel multi-step transformation synthetic route for the first time with polystyrene spheres as the template, followed by the combination of a facile homogeneous precipitation method, an ion-exchange process and a calcination process. The results show that the as-obtained YBO 3 : Eu 3+ /Tb 3+ hollow spheres have a uniform morphology with an average diameter of 1.65 µm and shell thickness of about 160 nm. When used as luminescent materials, the emission colours of YBO 3 : Eu 3+ /Tb 3+ samples can be tuned from red, through orange, yellow and green-yellow, to green by simply adjusting the relative doping concentrations of the activator ions under the excitation of ultraviolet light, which might have potential applications in fields such as light display systems and optoelectronic devices.
    Keywords: inorganic chemistry, materials science, nanotechnology
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 6
    Publication Date: 2018-05-09
    Description: Objectives We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis. Design We performed 16S rRNA gene analysis of gastric mucosal samples from 81 cases including superficial gastritis (SG), atrophic gastritis (AG), intestinal metaplasia (IM) and gastric cancer (GC) from Xi’an, China, to determine mucosal microbiome dysbiosis across stages of GC. We validated the results in mucosal samples of 126 cases from Inner Mongolia, China. Results We observed significant mucosa microbial dysbiosis in IM and GC subjects, with significant enrichment of 21 and depletion of 10 bacterial taxa in GC compared with SG (q〈0.05). Microbial network analysis showed increasing correlation strengths among them with disease progression (p〈0.001). Five GC-enriched bacterial taxa whose species identifications correspond to Peptostreptococcus stomatis , Streptococcus anginosus , Parvimonas micra , Slackia exigua and Dialister pneumosintes had significant centralities in the GC ecological network (p〈0.05) and classified GC from SG with an area under the receiver-operating curve (AUC) of 0.82. Moreover, stronger interactions among gastric microbes were observed in Helicobacter pylori -negative samples compared with H. pylori -positive samples in SG and IM. The fold changes of selected bacteria, and strengths of their interactions were successfully validated in the Inner Mongolian cohort, in which the five bacterial markers distinguished GC from SG with an AUC of 0.81. Conclusions In addition to microbial compositional changes, we identified differences in bacterial interactions across stages of gastric carcinogenesis. The significant enrichments and network centralities suggest potentially important roles of P. stomatis , D. pneumosintes , S. exigua , P. micra and S. anginosus in GC progression.
    Keywords: Open access, Editor's choice, Gut
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 7
    Publication Date: 2018-02-18
    Description: Objectives This study aim to investigate the incidence, timing and risk factors of metachronous pulmonary recurrence after curative resection in patients with rectal cancer. Design A retrospective cohort study. Setting This study was conducted at a tertiary referral cancer hospital. Participants A total of 404 patients with rectal cancer who underwent curative resection from 2007 to 2012 at Beijing Hospital were enrolled in this study. Interventions The pattern of recurrence was observed and evaluated. Primary and secondary outcome measures The incidence and timing of recurrences by site were calculated, and the risk factors of pulmonary recurrence were analysed. Results The 5-year disease-free survival for the entire cohort was 77.0%. The most common site of recurrence was the lungs, with an incidence of 11.4%, followed by liver. Median interval from rectal surgery to diagnosis of pulmonary recurrence was much longer than that of hepatic recurrence (20 months vs 10 months, P=0.022). Tumour location, pathological tumor-node-metastasis (TNM) stage and positive circumferential resection margin were identified as independent risk factors for pulmonary recurrence. A predictive model based on the number of risk factors identified on multivariate analysis was developed, 5-year pulmonary recurrence-free survival for patients with 0, 1, 2 and 3 risk factors was 100%, 90.4%, 77.3% and 70.0%, respectively (P〈0.001). Conclusions This study emphasised that the lung was the most common site of metachronous metastasis in patients with rectal cancer who underwent curative surgery. For patients with unfavourable risk profiles, a more intensive surveillance programme that could lead to the early detection of recurrence is strongly needed.
    Keywords: Open access, Gastroenterology and hepatology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 8
    Publication Date: 2018-02-27
    Description: Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common adenovirus vectors such as Ad5. However, baseline immunity to these vectors still exists in human populations. Traditional cloning of new adenovirus vaccine vectors is a long and cumbersome process that takes 2 months or more and that requires rare unique restriction enzyme sites. Here we describe a novel, restriction enzyme-independent method for rapid cloning of new adenovirus vaccine vectors that reduces the total cloning procedure to 1 week. We developed 14 novel adenovirus vectors from rhesus monkeys that can be grown to high titers and that are immunogenic in mice. All vectors grouped with the unusual adenovirus species G and show extremely low seroprevalence in humans. Rapid cloning of novel adenovirus vectors is a promising approach for the development of new vector platforms. Rhesus adenovirus vectors may prove useful for clinical development. IMPORTANCE To overcome baseline immunity to human and chimpanzee adenovirus vectors, we developed 14 novel adenovirus vectors from rhesus monkeys. These vectors are immunogenic in mice and show extremely low seroprevalence in humans. Rhesus adenovirus vectors may prove useful for clinical development.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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