S-Petasin, the Main Sesquiterpene of Petasites formosanus, Inhibits Phosphodiesterase Activity and Suppresses Ovalbumin-Induced Airway Hyperresponsiveness

S-Petasin is the main sesquiterpene of Petasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1–5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma. S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC50) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis, S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (Ki) of 25.3 and 18.1 μM, respectively. Both IC50 and Ki values for PDE3 were significantly greater than those for PDE4. S-Petasin (10–30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (Penh) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition, S-petasin (10–30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG2a level in serum of these mice. The PDE4H value of S-petasin was >300 μM; therefore, its PDE4H/PDE4L value was calculated to be >17. In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan

Research on work zone vehicle queuing behavior based on cellular automata

A model is proposed to estimate the work zone queue length, and the cellular automata based on empirical data is used for model validation. This estimation model can be applied to work zone organization and management to improve work zone capacity and security. Relationship between the average queue length and the warning zone length can be found, and the appropriate warning zone length can be determined according to design flow. Moreover, the appropriate work zone lane-changing strategies under different design flows are found through the estimation model

Inhibitory effects of armepavine against hepatic fibrosis in rats

Activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrogenesis. armepavine (Arm, C19H23O3N), an active compound from Nelumbo nucifera, has been shown to exert immunosuppressive effects on T lymphocytes and on lupus nephritic mice. The aim of this study was to investigate whether Arm could exert anti-hepatic fibrogenic effects in vitro and in vivo. A cell line of rat HSCs (HSC-T6) was stimulated with tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS) to evaluate the inhibitory effects of Arm. An in vivo therapeutic study was conducted in bile duct-ligated (BDL) rats. BDL rats were given Arm (3 or 10 mg/kg) by gavage twice daily for 3 weeks starting from the onset of BDL. Liver sections were taken for fibrosis scoring, immuno-fluorescence staining and quantitative real-time mRNA measurements. In vitro, Arm (1-10 μM) concentration-dependently attenuated TNF-α- and LPS-stimulated α-SMA protein expression and AP-1 activation by HSC-T6 cells without adverse cytotoxicity. Arm also suppressed TNF-α-induced collagen collagen deposition, NFκB activation and MAPK (p38, ERK1/2, and JNK) phosphorylations. In vivo, Arm treatment significantly reduced plasma AST and ALT levels, hepatic α-SMA expression and collagen contents, and fibrosis scores of BDL rats as compared with vehicle treatment. Moreover, Arm attenuated the mRNA expression levels of col 1α2, TGF-β1, TIMP-1, ICAM-1, iNOS, and IL-6 genes, but up-regulated metallothionein genes. Our study results showed that Arm exerted both in vitro and in vivo antifibrotic effects in rats, possibly through anti-NF-κB activation pathways

The Components of Flemingia macrophylla Attenuate Amyloid β-Protein Accumulation by Regulating Amyloid β-Protein Metabolic Pathway

Flemingia macrophylla (Leguminosae) is a popular traditional remedy used in Taiwan as anti-inflammatory, promoting blood circulation and antidiabetes agent. Recent study also suggested its neuroprotective activity against Alzheimer's disease. Therefore, the effects of F. macrophylla on Aβ production and degradation were studied. The effect of F. macrophylla on Aβ metabolism was detected using the cultured mouse neuroblastoma cells N2a transfected with human Swedish mutant APP (swAPP-N2a cells). The effects on Aβ degradation were evaluated on a cell-free system. An ELISA assay was applied to detect the level of Aβ1-40 and Aβ1-42. Western blots assay was employed to measure the levels of soluble amyloid precursor protein and insulin degrading enzyme (IDE). Three fractions of F. macrophylla modified Aβ accumulation by both inhibiting β-secretase and activating IDE. Three flavonoids modified Aβ accumulation by activating IDE. The activated IDE pool by the flavonoids was distinctly regulated by bacitracin (an IDE inhibitor). Furthermore, flavonoid 94-18-13 also modulates Aβ accumulation by enhancing IDE expression. In conclusion, the components of F. macrophylla possess the potential for developing new therapeutic drugs for Alzheimer's disease

Proline-Based Boronic Acid Receptors for Chiral Recognition of Glucose

Chiral recognition remains a major challenge in the area of molecular receptor design. With this research, we set out to explore the use of proline-based receptors for chiral recognition. Importantly, the proline structure allows for the introduction of at least two different binding groups due to the availability of both an amine and carboxylic acid group. Here we report a proof-of-concept exploration into the chiral recognition of d/l-glucose as a model chiral species, which prefers to bind to at least two boronic acid groups. We evaluated several proline-based receptors incorporating two phenylboronic acid groups, respectively, at the N- and C-termini of the amino acid residue, via amide bonds. We confirmed that the receptors exhibited chiral recognition using CD, 1H NMR, and 19F NMR spectroscopy. Given the derivation diversity available, our strategy to use proline-based receptors for chiral recognition holds significant promise for extension to other chiral systems. </p

A Comprehensive Analysis of Fermi Gamma-ray Burst Data: III. Energy-Dependent T90 Distributions of GBM GRBs and Instrumental Selection Effect on Duration Classification

The durations (T90) of 315 GRBs detected with Fermi/GBM (8-1000 keV) by 2011 September are calculated using the Bayesian Block method. We compare the T90 distributions between this sample and those derived from previous/current GRB missions. We show that the T90 distribution of this GRB sample is bimodal, with a statistical significance level being comparable to those derived from the BeppoSAX/GRBM sample and the Swift/BAT sample, but lower than that derived from the CGRO/BATSE sample. The short-to-long GRB number ratio is also much lower than that derived from the BATSE sample, i.e., 1:6.5 vs 1:3. We measure T90 in several bands, i.e., 8-15, 15-25, 25-50, 50-100, 100-350, and 350-1000 keV, to investigate the energy-dependence effect of the bimodal T90 distribution. It is found that the bimodal feature is well observed in the 50-100 and 100-350 keV bands, but is only marginally acceptable in the 25-50 keV and 350-1000 keV bands. The hypothesis of the bimodality is confidently rejected in the 8-15 and 15-25 keV bands. The T90 distributions in these bands are roughly consistent with those observed by missions with similar energy bands. The parameter T90 as a function of energy follows \bar T90 \propto E^{-0.20\pm 0.02} for long GRBs. Considering the erratic X-ray and optical flares, the duration of a burst would be even much longer for most GRBs. Our results, together with the observed extended emission of some short GRBs, indicate that the central engine activity time scale would be much longer than T90} for both long and short GRBs and the observed bimodal T90 distribution may be due to an instrumental selection effect.Comment: 29 pages, 2 tables, 9 figures, accepted for publication in Ap

Analysis of Genes Related to Angiotensin II-Induced Arterial Injury Using a Time Series Microarray

Background/Aims: Angiotensin II (Ang II)-mediated hypertension is a major risk factor for cardiovascular diseases. Ang II induces changes in vessel structure and function through the activation of genes related to signaling pathways. However, the changes in the gene expression profiles of blood vessels in response to Ang II remain unclear. Methods: Wild-type C57BL/6 mice were infused with Ang II (1500 ng/kg/min) using an osmotic pump for 1, 3, and 7 days. Vascular wall inflammation and remodeling were evaluated by pathological examination. Time-series microarray and quantitative PCR analyses were performed. Bioinformatics analyses were conducted to identify key genes, pathways, and biological processes. Results: After Ang II infusion, blood pressure and aortic remodeling were increased over time. Microarray analysis identified a totally of 3631 differentially expressed genes in aortas at days 1, 3, and 7 of Ang II infusion. These genes were involved in multiple biological processes, including cell adhesion, angiogenesis, cell migration, protein phosphorylation, immune system, and cell cycle, which may play important roles in regulating Ang II-induced arterial injury during hypertension. The genes were classified into 50 profiles by hierarchical cluster analysis, and finally, 14 significant profiles were identified. Among these genes, protein kinase cAMP-activated catalytic subunit alpha (Prkaca), a gene that directly regulated 137 neighboring genes, was located at the center of the gene network in Ang II-infused aortas. Further, Prkaca protein expression and cAMP level were downregulated in a time-dependent manner in Ang II-infused aortas. Conclusions: The combined use of DNA microarrays and cluster and gene network analyses identified Prkaca as a key Ang II-responsive gene that may mediate early vascular injury and hypertension

Synovial Macrophages: Past Life, Current Situation, and Application in Inflammatory Arthritis

Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients’ quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease

The Double-Time Green's Function Approach to the Two-Dimensional Heisenberg Antiferromagnet with Broken Bonds

We improved the decoupling approximation of the double-time Green's function theory, and applied it to study the spin-${1\over 2}$ two-dimensional antiferromagnetic Heisenberg model with broken bonds at finite temperature. Our decoupling approximation is applicable to the spin systems with spatial inhomogeneity, introduced by the local defects, over the whole temperature region. At low temperatures, we observed that the quantum fluctuation is reduced in the neighborhood of broken bond, which is in agreement with previous theoretical expectations. At high temperatures our results showed that the quantum fluctuation close to the broken bond is enhanced. For the two parallel broken bonds cases, we found that there exists a repulsive interaction between the two parallel broken bonds at low temperatures.Comment: Revtex, 6 pages, 5 Postscript figures (include