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•Natural compound isocampneoside II (ICD) was isolated from genus Paulownia.•ICD exhibited good antioxidant ability on superoxide radical scavenging activity, reducing power, and ...metal chelating.•ICD showed protective effect against oxidative protein damage induced by hydroxyl radicals.•ICD could ameliorate H2O2-induced oxidative stress and apoptosis in PC12 cells.•ICD inhibited cell apoptosis and Bax/Bcl-2 ratio induced by H2O2.
Oxidative stress has been considered as a major cause of cell damage in various neurodegenerative disorders. One of the reasonable strategies for delaying the disease’s progression is to prevent reactive oxygen species (ROS) mediated cellular injury by dietary or pharmaceutical augmentation of free radical scavengers. Isocampneoside II (ICD) is an active phenylethanoid glycoside isolated from the medicinal hardwood genus Paulownia. This study was designed to explore free radical scavenging potential of ICD in different in vitro systems and its protective role in hydrogen peroxide (H2O2)-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. The results showed ICD eliminated approximately 80.75% superoxide radical at the concentration of 0.1mg/ml and inhibited metal chelating by 22.07% at 8mg/ml. Additionally, ICD showed a strong ability on reducing power and provided protection against oxidative protein damage induced by hydroxyl radicals. Pretreatment of PC12 cells with ICD prior to H2O2 exposure elevated cell viability, enhanced activity of superoxide dismutase and catalase, and decreased levels of malondialdehyde and intracellular ROS. Furthermore, ICD inhibited cell apoptosis and Bax/Bcl-2 ratio induced by H2O2. These findings suggested ICD may be considered as a potential antioxidant agent and should encourage for further research in neurodegenerative diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•The 1:4-scale SNL PCCV model is numerically investigated in details.•Interactions between steel materials and concrete are implicitly accounted for.•Fracture energy based evolution laws for the ...stress and damage are employed.•Appropriate modifications of the material constitutive relations are presented.•Limit capacity and ultimate failure mode of the PCCV model can be captured.
This work addresses the numerical modeling and simulation of prestressed concrete containment vessels (PCCVs) using the damaged-plasticity model for concrete and accounting for its interactions with the steel materials (i.e., the steel rebars, liner plate and prestressed tendons). Specifically, the 1:4-scale PCCV model tested by the Sandia National Lab (SNL) is considered. For concrete a novel fracture energy based method is employed to produce the data for the softening curve and damage evolution law such that mesh size independent numerical results can be guaranteed. To facilitate the finite element modeling, the interactions between steel and concrete are indirectly modeled by modifying appropriately the stress-strain relations of the steel materials as in Hsu and Mo (2010). The SNL PCCV model is then numerically modeling and symmetrically investigated. The effects of various strategies in modifying the steel stress-strain relations are discussed. It is found that, in addition to the prestressed tendons, the interactions between the liner plate/steel bars and concrete play non-negligible roles in correctly predicting the limit capacity and ultimate failure mode of the PCCV model. The numerical results obtained from the presented method, i.e., the limit capacity, failure mode, deformations and strains around crucial locations, etc., agree well with the experimental data, illustrating its capability in modeling the mechanical behavior of the PCCV like structures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The primary challenge associated with the development of an LC/MS/MS-based assay for simultaneous determination of biogenic monoamine neurotransmitters such as norepinephrine (NE), dopamine (DA), ...serotonin (5-HT), and normetanephrine (NM) in rat brain microdialysates is to improve detection sensitivity. In this work, a UPLC/MS/MS-based method combined with a diethyl labeling technique was developed for simultaneous determination of a panel of monoamines in rat prefrontal cortex microdialysates. The chromatographic run time is 3.5 min/sample. The limits of detection of the UPLC/MS/MS-based method for NE, DA, 5-HT/ and NM, with/without diethyl labeling of monoamines, are 0.005/0.4 (30/2367 pM), 0.005/0.1 (33/653 pM), 0.005/0.2 (28/1136 pM), and 0.002/0.2 ng/mL (11/1092 pM), respectively. Diethyl labeling of amino groups of monoamines affords 20−100 times increased detection sensitivity of corresponding native monoamines during the UPLC/MS/MS analysis. This could result from the following: (1) improved fragmentation patterns; (2) increased hydrophobicity and concomitantly increased ionization efficiency in ESI MS and MS/MS analysis; (3) reduced matrix interference. This labeling reaction employs a commercially available reagent, acetaldehyde-d 4, to label the amine groups on the monoamines via reductive amination. It is also simple, fast (∼25-min reaction time), specific, and quantitative under mild reaction conditions. Data are also presented from the application of this assay to monitor the drug-induced changes of monoamine concentrations in rat prefrontal cortex microdialysate samples followed by administration of SKF 81297, a selective D1 dopamine receptor agonist known to elevate the extracellular level of the neurotransmitters DA and NE in the central nervous system.
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IJS, KILJ, NUK, PNG, UL, UM
Dysfunction of glomerular mesangial cells (GMCs) plays an important role in pathogenesis of diabetic nephropathy. Here, we investigated the effects of Dangguibuxue decoction (DBD), an herbal ...traditional Chinese medicinal (TCM) formula composed of Astragali Radix and Angelicae Sinensis Radix, on GMC proliferation and fibrogenesis under high-glucose (HG) conditions.
Sixty male Sprague Dawley rats were divided into 5 groups and administered intragastric 0.9% saline, low concentration DBD (DBD-L, 1.75 g/kg/d), middle concentration DBD (DBD-M, 3.5 g/kg/d), high concentration DBD (DBD-H, 7.0 g/kg/d) and gliclazide (GL, 2 mg/kg/d), respectively, for 1 week, and then their sera were obtained. Rat mesangial cells (HBZY-1 cells) were treated with these sera under HG condition (30 mmol/L).
The proliferation of GMCs under HG conditions was significantly greater than that under normal glucose condition. Low concentration DBD (DBD-L) inhibited proliferation of GMCs after 72-h incubation (P < 0.01), while high concentration DBD (DBD-H) inhibited GMCs proliferation at 24, 48 and 72 time points (P < 0.01). There was no significant difference between the inhibitory effect of DBD-H and GL sera on GMC proliferation (P > 0.05). Furthermore, all concentrations of DBD (DBD-L, DBD-M and DBD-H) significantly decreased the protein expression of α-SMA(α-smooth muscle actin) (P < 0.01), an indicator of interstitial fibrosis of GMCs. Finally, DBD-L, DBD-M, DBD-H sera obviously inhibited the increase of HYP (hydroxyproline)secretion under HG condition (P < 0.01).
Our results demonstrate an inhibitory effect of DBD extract on proliferation and fibrogenesis of GMCs under HG conditions. The potential role of DBD in the treatment of diabetic neuropathy merits further investigation.
Phytochemical investigation of branch wood of
Lambert resulted in the isolation of a new lignan glycoside, which was named phillyrin-6″-α-rhamnoside. The structure of the new compound was mainly ...elucidated by chemical and spectral evidence including 2D nuclear magnetic resonance studies. In addition, four known phenolics, including a phenylpropanoid glucoside (trans-isoconiferin), a phenolic acid (caffeic acid), a neolignan (cedrusin), and a lignan glucoside (phillyrin), were reported for the first time to be present in
A new natural compound, esculetin-5-O-β-D-glucopyranoside (1), along with two known flavonoids, quercetin (2) and kaempferol-3-β-D-glucopyranoside (3), was purified from the heartwood of Fraxinus ...velutina. Their chemical structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR, and MS techniques.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Excessive dermal scarring is characterized by an overabundant deposition of extracellular matrix caused by fibrosis. The purpose of this study was to modify a rodent model of cutaneous healing for ...use in the development of compounds to minimize scarring, and to test the model with a small molecule inhibitor of transforming growth factor-β type I receptor, activin receptor-like kinase 5, because this class of inhibitors has been demonstrated to be effective in minimizing fibrosis in other organs.
The rodent model of cutaneous healing consists of uniform full-thickness incisional dermal wounds in rats. Wounds were allowed to heal by secondary intention, generally over a 14-day period. The usefulness of the model was tested by the application of an activin receptor-like kinase 5 inhibitor, CP-639180. Activin receptor-like kinase 5 inhibition antagonizes the transforming growth factor-β pathway, and was used to determine whether there was an effect on collagen deposition in wounds. The compound was applied once per day for 7 days starting at postwounding day 0 or 7 (early or late treatment regimens). Wounds were analyzed histologically for collagen deposition and biochemically for quantification of collagen changes.
Early and late treatment regimens with the activin receptor-like kinase 5 inhibitor significantly reduced collagen deposition without impairing wound healing.
Application of a small molecular inhibitor of activin receptor-like kinase 5 appears to significantly reduce collagen deposition in rat dermal wounds as reported here for the first time. Activin receptor-like kinase 5 inhibition may offer a novel approach to reducing proliferative scars in humans because collagen accumulation is a core event in scarring.
Brain edema formation during the early stages of focal cerebral ischemia is associated with an increase in both sodium content and blood-brain barrier (BBB) sodium transport. The goals of this study ...were to determine whether chloride is the principal anion that accumulates in ischemic brain, how the rate of BBB transport of chloride compares with its rate of accumulation, and whether the stimulation seen in BBB sodium transport is also seen with other cations. Focal ischemia was produced by occlusion of the middle cerebral artery (MCAO) in anesthetized rats. Over the first 6 h after MCAO, the amount of brain water in the center of the ischemic cortex increased progressively at a rate of 0.15 +/- 0.02 (SE) g/g dry wt/h. This was accompanied by a net increase in brain sodium (48 +/- 12 mumol/g dry wt/h) and a loss of potassium (34 +/- 7 mumol/g dry wt/h). The net rate of chloride accumulation (16 +/- 1 mumol/g dry wt/h) approximated the net rate of increase of cations. Three hours after MCAO, the BBB permeability to three ions (22Na, 36Cl, and 86Rb) and two passive permeability tracers (3Halpha-aminoisobutyric acid (3HAIB) and 14Curea) was determined. Permeability to either passive tracer was not increased, indicating that the BBB was intact. The rate of 36Cl influx was 3 times greater and the rate of 22Na influx 1.8 times greater than their respective net rates of accumulation in ischemic brain.
: The mechanism of unidirectional transport of glutamine from blood to brain in pentobarbital‐anesthetized rats was examined using in situ perfusion. Amino acid uptake into brain across the ...blood‐brain barrier (BBB) is classically thought to be via the Na‐independent large neutral (L‐system), acidic and basic amino acid transporters. In the presence of physiological concentrations of amino acids in the perfusate, which should saturate the known amino acid transporters at the BBB, the cortical transfer constant (Ki) for l‐14Cglutamine was 11.6 ± 1.1 µl/g/min. The addition of either 10 mM 2‐amino‐2‐norbornanecarboxylic acid or 10 mM 2‐amino‐2‐norbornanecarboxylic acid and 5 mM cysteine had no effect on the cortical Ki for l‐14Cglutamine, indicating that glutamine transport under these conditions does not occur by the L‐, A‐, or ASC‐systems. Decreasing perfusate Na from 140 to 2.4 mM by Tris substitution reduced the cortical Ki for l‐14Cglutamine by 62% (p≤ 0.001). The Na‐dependent uptake has the characteristics of N‐system transport. It was inhibited by l‐histidine and l‐glutamine, both N‐system substrates, and it was pH sensitive and moderately tolerant of Li substitution for Na. This putative N‐system transporter at the luminal membrane of the BBB plays an important role in mediating brain glutamine uptake.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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