2,905 research outputs found

    Protective Effects of Costunolide Against D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice

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    Costunolide, a sesquiterpene isolated from Vladimiria souliei (Franch.) Ling, is known to exhibit anti-inflammatory, anti-viral, and anti-tumor activities. However, the effects of costunolide on liver injury are poorly understood. The current study aimed to investigate the hepatoprotective effects of costunolide against lipopolysaccharide (LPS) and D-galactosamine-induced acute liver injury (ALI) in mice. The results indicated that costunolide (40 mg/kg) could significantly improve the pathological changes of hepatic tissue, and reduced the LPS and D-galactosamine-induced increases of alanine aminotransferase (from 887.24 ± 21.72 to 121.67 ± 6.56 IU/L) and aspartate aminotransferase (from 891.01 ± 45.24 to 199.94 ± 11.53 IU/L) activities in serum. Further research indicated that costunolide significantly reduced malondialdehyde content (from 24.56 ± 1.39 to 9.17 ± 0.25 nmol/ml) and reactive oxygen species (from 203.34 ± 7.68 to 144.23 ± 7.12%), increased the activity of anti-oxidant enzymes superoxide dismutase (from 153.74 ± 10.33 to 262.27 ± 8.39 U/ml), catalase (from 6.12 ± 0.30 to 12.44 ± 0.57 U/ml), and total anti-oxidant capacity (from 0.64 ± 0.06 to 6.29 ± 0.11 U/ml) in hepatic tissues. Western blot results revealed that costunolide may trigger the anti-oxidative defense system by inhibiting kelch-like ECH-associated protein 1 and nuclear factor-related factor 2 (cytosol), increasing nuclear factor-related factor 2 (nucleus), heme oxygenase-1 and NAD (P) H quinone oxidoreductase 1 activity. Moreover, costunolide significantly decreased the protein expression of proinflammatory cytokines including interleukin 1β, interleukin 6, and tumor necrosis factor. Pretreatment with costunolide could reduce the expression of toll-like receptor 4, myeloid differentiation factor 88, p65 (Nucleus), phosphorylated IκB kinase α/β, inhibitor of nuclear factor kappa-B kinase, inhibitor kappa Bα and prevent the expression of phosphorylated inhibitor kappa B kinase which repressed translocation of p65 from cytoplasm to nucleus. In addition, pretreatment with costunolide also inhibited hepatocyte apoptosis by reducing the expression of B-cell lymphoma 2 associated X, cytochrome C, cysteinyl aspartate specific proteinase 3, cysteinyl aspartate specific proteinase 8 and cysteinyl aspartate specific proteinase 9, and by increasing B-cell lymphoma 2. From the above analysis, the protective effects of costunolide against LPS and D-galactosamine-induced ALI in mice may be attributed to its anti-oxidative activity in nuclear factor-related factor 2 signaling pathways, anti-inflammatory suppression in nuclear factor-kappa B signaling pathways, and inhibition of hepatocyte apoptosis. Thus, costunolide may be a potential therapeutic agent in attenuating LPS and D-galactosamine -induced ALI in the future

    Visible Light Excited Catalysis and Reusability Performances of TiO 2

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    To get high efficiency photodegradation on pollutants under visible light, Pr(III) doped Y2SiO5 upconversion materials and anatase TiO2 nanofilm coated Pr:Y2SiO5 composite have been prepared by using a sol-gel method. XRD and SEM test results indicated that TiO2 nanofilm was well coated on Pr:Y2SiO5 to form TiO2@Pr:Y2SiO5 composite particles with the sizes of 0.5–1.0 μm. To avoid secondary pollution resulting from incomplete recovery of catalyst particles, TiO2@Pr:Y2SiO5 was loaded on the glass fiber filters by using a dip-coating method. It is found that the catalyst particles were embedded into the carrier firmly, even after having been reused for 6 times. The luminescence intensities of TiO2@Pr:Y2SiO5 were getting down sharply with the coating contents of TiO2 increased, which was attributed to the adsorption of the luminescence by the TiO2 film in situ. As a result, TiO2@Pr:Y2SiO5 with 4% TiO2, which presented lowest luminescence intensity, showed the highest efficiency on the photodegradation of nitrobenzene wastewater. The catalysts loaded on glass fiber filters showed excellent reusability on the photodegradation of nitrobenzene and presented a photodegradation rate of 95% at the first time and up to 75.9% even after 6 times of reusing by the treatment time of 12 h

    Construction of α,α‐disubstituted α‐Amino Acid Derivatives via aza‐Morita‐Baylis‐Hillman Reactions of 2‐Aminoacrylates with Activated Olefins

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    A useful and convenient strategy for the synthesis of α,α‐disubstituted α‐amino acid (α‐AA) derivatives via aza‐Morita‐Baylis‐Hillman reaction of 2‐aminoacrylates with activated olefins has been developed. A variety of α‐AA derivatives containing an α‐amino tertiary center were synthesized in good to excellent yields. The kinetic profiles and calculated methyl anion affinity (MAA) values were employed to rationalize the reactivities of different Michael acceptors used in the reaction

    Hidden non-collinear spin-order induced topological surface states

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    Rare-earth monopnictides are a family of materials simultaneously displaying complex magnetism, strong electronic correlation, and topological band structure. The recently discovered emergent arc-like surface states in these materials have been attributed to the multi-wave-vector antiferromagnetic order, yet the direct experimental evidence has been elusive. Here we report the observation of non-collinear antiferromagnetic order with multiple modulations using spin-polarized scanning tunneling microscopy. Moreover, we discover a hidden spin-rotation transition of single-to-multiple modulations 2 K below the Neel temperature. The hidden transition coincides with the onset of the surface states splitting observed by our angle-resolved photoemission spectroscopy measurements. Single modulation gives rise to a band inversion with induced topological surface states in a local momentum region while the full Brillouin zone carries trivial topological indices, and multiple modulation further splits the surface bands via non-collinear spin tilting, as revealed by our calculations. The direct evidence of the non-collinear spin order in NdSb not only clarifies the mechanism of the emergent topological surface states, but also opens up a new paradigm of control and manipulation of band topology with magnetism.Comment: 32 pages, 4 figures, 10 extended figure

    Risk of pneumocystosis after early discontinuation of prophylaxis among HIV-infected patients receiving highly active antiretroviral therapy

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    <p>Abstract</p> <p>Background</p> <p>Risk of pneumocystosis after discontinuation of primary or secondary prophylaxis among HIV-infected patients before CD4 counts increase to ≧200 cells/μL (early discontinuation) after receiving highly active antiretroviral therapy (HAART) is rarely investigated.</p> <p>Methods</p> <p>Medical records of 660 HIV-infected patients with baseline CD4 counts <200 cells/μL who sought HIV care and received HAART at a university hospital in Taiwan between 1 April, 1997 and 30 September, 2007 were reviewed to assess the incidence rate of pneumocystosis after discontinuation of prophylaxis for pneumocystosis.</p> <p>Results</p> <p>The incidence rate of pneumocystosis after HAART was 2.81 per 100 person-years among 521 patients who did not initiate prophylaxis or had early discontinuation of prophylaxis, which was significantly higher than the incidence rate of 0.45 per 100 person-years among 139 patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL (adjusted risk ratio, 5.32; 95% confidence interval, 1.18, 23.94). Among the 215 patients who had early discontinuation of prophylaxis after achievement of undetectable plasma HIV RNA load, the incidence rate of pneumocystosis was reduced to 0.31 per 100 person-years, which was similar to that of the patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL (adjusted risk ratio, 0.63; 95% confidence interval, 0.03, 14.89).</p> <p>Conclusions</p> <p>Compared with the risk of pneumocystosis among patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL after HAART, the risk was significantly higher among patients who discontinued prophylaxis when CD4 counts remained <200 cells/μL, while the risk could be reduced among patients who achieved undetectable plasma HIV RNA load after HAART.</p

    In Vivo Disruption of TGF-β Signaling by Smad7 in Airway Epithelium Alleviates Allergic Asthma but Aggravates Lung Carcinogenesis in Mouse

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    BACKGROUND: TGF-beta has been postulated to play an important role in the maintenance of epithelial homeostasis and the development of epithelium-derived cancers. However, most of previous studies are mainly focused on the function of TGF-beta in immune cells to the development of allergic asthma and how TGF-beta signaling in airway epithelium itself in allergic inflammation is largely unknown. Furthermore, the in vivo TGF-beta function specifically in the airway epithelium during lung cancer development has been largely elusive. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the in vivo contribution of TGF-beta signaling in lung epithelium to the development of allergic disease and lung cancer, we generated a transgenic mouse model with Smad7, an intracellular inhibitor of TGF-beta signaling, constitutively expressed in mouse airway Clara cells using a mouse CC10 promoter. The mice were subjected to the development of OVA-induced allergic asthma and urethane-induced lung cancer. The Smad7 transgenic animals significantly protected from OVA-induced asthma, with reduced airway inflammation, airway mucus production, extracellular matrix deposition, and production of OVA-specific IgE. Further analysis of cytokine profiles in lung homogenates revealed that the Th2 cytokines including IL-4, IL-5 and IL-13, as well as other cytokines including IL-17, IL-1, IL-6, IP10, G-CSF, and GM-CSF were significantly reduced in the transgenic mice upon OVA induction. In contrast, the Smad7 transgenic animals had an increased incidence of lung carcinogenesis when subjected to urethane treatment. CONCLUSION/SIGNIFICANCE: These studies, therefore, demonstrate for the first time the in vivo function of TGF-beta signaling specifically in airway epithelium during the development of allergic asthma and lung cancer

    Impact of residual and intrafractional errors on strategy of correction for image-guided accelerated partial breast irradiation

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    <p>Abstract</p> <p>Background</p> <p>The cone beam CT (CBCT) guided radiation can reduce the systematic and random setup errors as compared to the skin-mark setup. However, the residual and intrafractional (RAIF) errors are still unknown. The purpose of this paper is to investigate the magnitude of RAIF errors and correction action levels needed in cone beam computed tomography (CBCT) guided accelerated partial breast irradiation (APBI).</p> <p>Methods</p> <p>Ten patients were enrolled in the prospective study of CBCT guided APBI. The postoperative tumor bed was irradiated with 38.5 Gy in 10 fractions over 5 days. Two cone-beam CT data sets were obtained with one before and one after the treatment delivery. The CBCT images were registered online to the planning CT images using the automatic algorithm followed by a fine manual adjustment. An action level of 3 mm, meaning that corrections were performed for translations exceeding 3 mm, was implemented in clinical treatments. Based on the acquired data, different correction action levels were simulated, and random RAIF errors, systematic RAIF errors and related margins before and after the treatments were determined for varying correction action levels.</p> <p>Results</p> <p>A total of 75 pairs of CBCT data sets were analyzed. The systematic and random setup errors based on skin-mark setup prior to treatment delivery were 2.1 mm and 1.8 mm in the lateral (LR), 3.1 mm and 2.3 mm in the superior-inferior (SI), and 2.3 mm and 2.0 mm in the anterior-posterior (AP) directions. With the 3 mm correction action level, the systematic and random RAIF errors were 2.5 mm and 2.3 mm in the LR direction, 2.3 mm and 2.3 mm in the SI direction, and 2.3 mm and 2.2 mm in the AP direction after treatments delivery. Accordingly, the margins for correction action levels of 3 mm, 4 mm, 5 mm, 6 mm and no correction were 7.9 mm, 8.0 mm, 8.0 mm, 7.9 mm and 8.0 mm in the LR direction; 6.4 mm, 7.1 mm, 7.9 mm, 9.2 mm and 10.5 mm in the SI direction; 7.6 mm, 7.9 mm, 9.4 mm, 10.1 mm and 12.7 mm in the AP direction, respectively.</p> <p>Conclusions</p> <p>Residual and intrafractional errors can significantly affect the accuracy of image-guided APBI with nonplanar 3DCRT techniques. If a 10-mm CTV-PTV margin is applied, a correction action level of 5 mm or less is necessary so as to maintain the RAIF errors within 10 mm for more than 95% of fractions. Pre-treatment CBCT guidance is not a guarantee for safe delivery of the treatment despite its known benefits of reducing the initial setup errors. A patient position verification and correction during the treatment may be a method for the safe delivery.</p
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