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Five unknown labdane diterpenoids Stevelin A-E (1-5), three known labdane diterpenoids (6-8) and three labdane norditerpenoids (9-11) were isolated from the Stevia rebaudiana. The structures were determined primarily via NMR spectroscopic data and HRESIMS experiments. X-ray crystallography using Cu Kα radiation was used to determine the absolute configurations of 1, and the absolute configurations of 2-5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti-atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis..

Enterovirus 71 (EV71) is the predominant pathogen for severe hand, foot, and mouth disease (HFMD) in children younger than 5 years, and currently no effective drugs are available for EV71. Thus, there is an urgent need to develop new drugs for the control of EV71 infection. In this study, LJ04 was extracted from Laminaria japonica using diethylaminoethyl cellulose-52 with 0.4 mol/l NaCl as the eluent, and its virucidal activity was evaluated based on its cytopathic effects on a microplate. LJ04 is composed of fucose, galactose, and mannose and mainly showed good virucidal activity against EV71. The antiviral mechanisms of LJ04 were the direct inactivation of the virus, the blockage of virus binding, disruptions to viral entry, and weak inhibitory activity against the nonstructural protein 3C. The two most important findings from this study were that LJ04 inhibited EV71 proliferation in HM1900 cells, which are a human microglia cell line, and that LJ04 can directly inactivate EV71 within 2 hr at 37°C. This study demonstrates for the first time the ability of a polysaccharide from L. japonica to inhibit viral and 3C activity; importantly, the inhibition of 3C might have a minor effect on the antiviral effect of LJ04. Consequently, our results identify LJ04 as a potential drug candidate for the control of severe EV71 infection in clinical settings.

A novel series of pyrazine-1,3-thiazine hybrid conjugates were synthesized in excellent yield. These derivatives were subsequently tested against human immunodeficiency virus (HIV-1); hemagglutinin type 1 and neuraminidase type 1-'influenza' A (H1N1) virus; enterovirus 71 (EV71); and coxsackievirus B3. The effect of these conjugates on the key enzymes responsible for the progression of these viral infections was also illustrated via enzyme-based assay, such as HIV-1 reverse transcriptase (RT) and neuraminidase, where entire tested molecules showed considerable inhibition. Particularly, among the tested derivatives, compound 3k was identified as most promising inhibitor of HIV-1 with 94% of inhibition (IC50 3.26 ± 0.2 μm). Moreover, the compound 3d was found to be the most potent analogue to inhibit the H1N1 virus with IC50 of 5.32 ± 0.4 μm together with inhibition of the neuraminidase enzyme (IC50 11.24 ± 1.1 μm). In regard to inhibitory activity against enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the tested derivatives showed considerable inhibition of infection. Molecular docking studies were also performed for the most promising inhibitors with their corresponding target protein to exemplify the structural requirement for better inhibitory activity. The results of inhibitory assay showed that designed molecules possess considerable inhibitory activity against the virus tested.

Trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) has been reported to induce body fat loss with the side effects of liver steatosis and the development of diabetes. To investigate whether the dietary fat content may influence the response to t10c12-CLA in animals, t10c12-producing recombinant food-grade Lactococcus lactis transformed with the pai isomerase gene was used to feed lean, obesity-induced, or obese mice. Compared with the non-CLA producing recombinant, the significant (p

BACKGROUND: Stimuli-sensitive materials show enormous potential in the development of drug delivery systems. But the low response rate of most stimuli-sensitive materials limits their wider application. We propose that electrospinning, a technique for the preparation of ultrafine fibrous materials with ultrafine diameters, may be used to prepare materials with a fast response to stimuli. RESULTS: Poly[styrene-co-(maleic sodium anhydride)] and cellulose (SMA-Na/cellulose) hydrogel nanofibers were prepared through hydrolysis of precursor electrospun poly[styrene-co-(maleic anhydride)]/cellulose acetate (SMA/CA) nanofibers. In the presence of diethylene glycol, the SMA/CA composite nanofibers were crosslinked by esterification at 145 °C, and then hydrolyzed to yield crosslinked SMA-Na/cellulose hydrogel nanofibers. These nanofibers showed better mechanical strengths and were pH responsive. Their water swelling ratio showed a characteristic two-step increase at pH = 5.0 and 8.2, with the water swelling ratio reaching a maximum of 27.6 g g−1 at pH = 9.1. CONCLUSION: The crosslinked SMA-Na hydrogel nanofibers supported on cellulose showed improved dimensional stability upon immersion in aqueous solutions. They were pH responsive. This new type of hydrogel nanofiber is a potential material for biomedical applications. Copyright © 2009 Society of Chemical Industry

Purpose To investigate delayed hyperenhancement during different healing stages of myocardial infarct with and without reperfusion in a pig model. Materials and Methods Twelve pigs were studied. Six pigs were subjected to permanent right coronary artery (RCA) occlusion, and the other six were subjected to transient 90-minute RCA occlusion. In vivo MRI including first-pass perfusion and myocardial delayed enhancement (MDE) was performed at four, eight, 12, and 24 hours, and eight days after the artery occlusion. The MDE scan was repeated four times, two to 32 minutes after contrast administration. Results For all six pigs without reperfusion, the four-hour MRI showed transmural perfusion defect and no delayed hyperenhancement; from eight hours on, delayed hyperenhancement appeared and its spatial extent gradually increased until it became transmural hyperenhancement at eight days. However, in all six pigs with reperfusion, hyperenhancement was present at every stage from four hours to eight days. Pathology confirmed the existence of infarct at various stages of healing irrespective of reperfusion status. Conclusion Occlusive hyperacute infarct did not exhibit any delayed hyperenhancement, which indicates that perfusion plays an important role in delayed enhancement at the hyperacute stage. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

We prospectively evaluated metabolite changes in late delayed radiation-induced injury to the temporal lobes on proton ((1)H) magnetic resonance spectroscopy (MRS) in 34 patients. Morphologically more severe injury on imaging tended to have lower N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) ratios. A significantly higher Cho/Cr ratio was found in the most severe grade of cerebral necrosis, in which lactate might be present. The progressive decrease in NAA with increasing severity reflected neuronal loss at different stages of late delayed radiation-induced brain injury. The absence of Cho elevation in mild and moderate lesions did not suggest demyelination or glial hyperplasia as an etiologic mechanism of late delayed radiation-induced brain injury. The association of severe morphologic lesions with elevated lactate suggests ischemia as the underlying mechanism for severe lesions. (1)H MRS may provide metabolite information conducive to the understanding of the pathophysiology of late radiation-induced brain injury. J. Magn. Reson. Imaging 1999;10:130-137.

CNR studies were performed for human intracranial vessels in 3D MRA data sets. The CNR dependency of different imaging parameters, such as flip angle, field of view, echo time, repetition time, and echo readout symmetry, was studied for vessels in the region of the circle of Willis. A theoretical model was developed for MR vascular imaging based on the Bloch equations and Fourier imaging theory. This model predicts the MR image intensity of vessels from basic subject parameters, such as the relaxation times of blood and stationary tissue, vessel dimension, and flow velocity, and the parameters of the imaging technique, such as flip angle, voxel volume, repetition time, and echo time. For most experiments, the model was found to fit the experimental results well. The validity of this model allows the optimization of imaging parameters to maximize vessel CNR in MR angiography.

To achieve correct spatial location of blood vessels, first order gradient moment nulling applied to the phase encoding axes can be used. However, gradient moment nulling prolongs echo time (TE), which may degrade the flow image in regions of complex flow. The fact that abbreviated moment compensated phase-encoding (AMCPE) can be used to apply partial flow compensation to the phase-encoding axes to prevent spatial misregistration of vessels without requiring the use of long echo times or using arbitrary chosen TE is demonstrated. AMCPE defines two cutoff lines in k-space. The flow-induced phase is completely compensated for values between the cutoff lines and partially compensated beyond the cutoff lines. The AMCPE technique has been tested on both a flow phantom and a human volunteer. The AMCPE images from both the in vivo and the in vitro study demonstrate correctly imaged flow. Computer simulations have been performed to analyze the penalty caused by the incomplete flow compensation. The result shows that the ripple artifacts due to the incomplete flow compensation are unobservable when 60%-70% of k-space is completely flow compensated.

The 21 S complex of enzymes for DNA synthesis in the combined low salt nuclear extract-post microsomal supernatant from HeLa cells [Malkas et al. (1990) Biochemistry 29:6362-6374] was purified by poly (ethylene glycol) precipitation, Q-Sepharose chromatography, Mono Q Fast Protein Liquid Chromatography (FPLC), and velocity gradient centrifugation. The procedure gives purified enzyme complex at a yield of 45%. The 21 S enzyme complex remains intact and functional in the replication of simian virus 40 DNA throughout the purification. Sedimentation analysis showed that the 21 S enzyme complex exists in the crude HeLa cell extract and that simian virus 40 in vitro DNA replication activity in the cell extract resides exclusively with the 21 S complex. The results of enzyme and immunological analysis indicate that DNA polymerase alpha-primase, a 3',5' exonuclease, DNA ligase I, RNase H, and topoisomerase I are associated with the purified enzyme complex. Denaturing polyacrylamide gel electrophoresis of the purified enzyme complex showed the presence of about 30 polypeptides in the size range of 300 to 15 kDa. Immunofluorescent imaging analysis, with antibodies to DNA polymerase alpha,beta and DNA ligase I, showed that polymerase alpha and DNA ligase I are localized to granular-like foci within the nucleus during S-phase. In contrast, DNA polymerase beta, which is not associated with the 21 S complex, is diffusely distributed throughout the nucleoplasm.